Listeriosis

MONDO:0005828 Pathograph 25 Show in embeddings browser bacterial infectious disease foodborne illness

A foodborne infection by Listeria monocytogenes, a Gram-positive bacterium that grows in the refrigerator and lives inside host cells. Most people who eat it are never diagnosed. In the old, the immunosuppressed, the pregnant and the newborn it invades, and then it presents as bacteraemia, as meningitis or meningoencephalitis, or as maternal-fetal infection ending in miscarriage, stillbirth or neonatal sepsis. The mechanism is a sequence of borrowed host machinery: internalins to get into the cell, listeriolysin O to get out of the vacuole, ActA to move by polymerising the host's own actin, and cell-to-cell spread that keeps the organism out of the extracellular space where antibody and complement wait. That intracellular lifestyle is also why the immunity that controls it is T cell mediated, and why pregnancy, which damps Th1 responses, is the risk factor it is.

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7
Pathophys.
11
Phenotypes
1
Gaps
25
Pathograph
3
Medical Actions
3
Subtypes
2
Datasets
3
Models
7
References
1
Deep Research
◆

Subtypes

3
Early-onset neonatal listeriosis
Disease presenting within the first six days of life, acquired in utero across an infected placenta. It presents with respiratory distress, sepsis, pneumonia, skin lesions or meningitis, is common in preterm infants, and carries the greater risk of severe complications and death of the two neonatal forms.
  • Granulomatosis Infantisepticum
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"Early-onset disease, occurring within the first 6 days of life, is characterized by symptoms such as respiratory distress, sepsis, pneumonia, skin lesions, or meningitis."
Defines the timing and the presenting features of this subtype.
Granulomatosis infantisepticum
The severe disseminated form of early-onset neonatal disease. Granulomas form throughout the liver, spleen, lung, kidney, brain and skin, red or blue-grey cutaneous nodules and papules are visible at or shortly after birth, and mortality reaches 80% in preterm infants. It is close to specific for this organism.
Show evidence (3 references)
PMID:39458411 SUPPORT Human Clinical
"A severe form of early-onset neonatal listeriosis is granulomatosis infantisepticum. This condition is characterized by the widespread formation of granulomas in various organs and tissues of the fetus or newborn, including the liver, spleen, lungs, kidneys, brain, and skin."
Defines the subtype and the organs the granulomas occupy.
PMID:39458411 SUPPORT Human Clinical
"Granulomatosis infantisepticum is associated with a high mortality rate, which can reach up to 80%, particularly among preterm infants."
Gives the mortality figure that distinguishes this subtype from ordinary early-onset disease.
PMID:39458411 SUPPORT Human Clinical
"A hallmark of this condition is the presence of distinctive skin lesions, which may appear as nodules or papules that are red or blue-gray in color."
Records the cutaneous sign by which the subtype is recognised at the bedside.
Late-onset neonatal listeriosis
Disease presenting between seven and twenty-eight days after birth, more often acquired around delivery than in utero. It presents with lethargy, drowsiness, vomiting or meningitis. It is less immediately fatal than the early-onset form and carries a risk of long-term neurological sequelae in survivors of meningitis.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"Late-onset disease typically develops between 7 and 28 days after birth, presenting with symptoms including lethargy, drowsiness, vomiting, or meningitis."
Defines the timing and the presenting features of this subtype.
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Discussions and Knowledge Gaps

1
Does the internalin A arm of intestinal invasion, established in guinea pigs and in mice carrying humanised E-cadherin, hold in the human gut, and how much of the older mouse literature on oral listeriosis is host-artefact?
HUMAN MODEL MISMATCH OPEN murine_e_cadherin_model_mismatch
Attached to
pathophysiology#Intestinal Epithelial Invasion by Internalins pathophysiology#Placental Infection and Fetal Compromise
Internalin A binds human E-cadherin and does not bind the murine protein, and one residue of E-cadherin decides it. Decades of oral-infection work in conventional mice therefore cannot speak to this step, and the evidence that it operates in vivo comes from the guinea pig and from a knock-in mouse engineered to carry the human receptor. Both are constructions designed to remove the mismatch, so the human claim rests on animals chosen or built for the purpose rather than on direct human observation. The mismatch is mechanistically load-bearing here because the same internalins are asserted to carry the organism across the placental and blood-brain barriers, and the human evidence for those crossings is a review statement rather than an experiment.
Proposed experiments
Internalin A dependent invasion in human intestinal organoids
listeriosis_inla_human_intestinal_organoid
Infect human intestinal organoids and primary enterocytes with wild-type and inlA deletion strains, and run the same comparison in the humanised E-cadherin knock-in mouse. The question is whether the engineered host reproduces the human tissue, or only the human receptor.
Decision criterion
The inlA deletion strain shows the same relative loss of invasion in human organoids as it does in the humanised knock-in mouse.
Would support
pathophysiology#Intestinal Epithelial Invasion by Internalins
Supporting outcome
  • Concordant inlA dependence in human tissue and in the humanised mouse would make the mouse result transferable to the human gut.
Refuting outcome
  • A human-tissue invasion phenotype that does not depend on inlA would mean the knock-in restores the receptor without restoring the human mechanism.
Show evidence (1 reference)
PMID:11387478 SUPPORT Model Organism
"In guinea pigs and transgenic mice expressing human E-cadherin, internalin was found to mediate invasion of enterocytes and crossing of the intestinal barrier."
This is the result the experiment is designed to test for transferability. It was obtained in two engineered or selected hosts and not in human tissue.
Trophoblast-stratified invasion in human placental explants
listeriosis_inla_placental_explant_trophoblast
Assay internalin binding and bacterial invasion in human placental explants, separating cytotrophoblast from syncytiotrophoblast, to test the reported susceptibility difference directly in human tissue rather than by inference from the mouse.
Decision criterion
Invasion is measurable in cytotrophoblast and absent or markedly lower at the syncytiotrophoblast surface.
Would support
pathophysiology#Placental Infection and Fetal Compromise
Supporting outcome
  • A cytotrophoblast-restricted invasion pattern in human tissue would ground the tropism claim without relying on an engineered host.
Refuting outcome
  • Equal invasion of both populations would mean the entry's trophoblast distinction is a cell-culture artefact.
Show evidence (1 reference)
PMID:39458411 SUPPORT In Vitro
"Syncytiotrophoblast cells are resistant to LM adhesion on their surface, whereas cytotrophoblast cells remain susceptible"
The claim this experiment would test in human placental tissue. As cited it rests on cultured cells rather than on explants.
Show evidence (1 reference)
PMID:10406800 SUPPORT In Vitro
"Here we show that mouse E-cadherin, although very similar to human E-cadherin (85% identity), is not a receptor for internalin."
States the receptor mismatch that makes this a model-fidelity question rather than an evidence gap.
⚙

Pathophysiology

7
Intestinal Epithelial Invasion by Internalins
InlA and InlB are surface proteins with leucine-rich repeats that bind host receptors and drive the bacterium into a cell that is not a phagocyte. InlA binds E-cadherin. The same family of proteins later carries the organism across the placental and blood-brain barriers, which is why one mechanism explains three tissue tropisms.
intestinal epithelial cell CL:0002563 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves intestinal epithelial cell (CL:0002563). CL:0002563 is a cell type from the Cell Ontology.
symbiont entry into host cell GO:0046718 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased symbiont entry into host cell (GO:0046718). GO:0046718 is a biological process from the Gene Ontology. ↑ INCREASED
Animal models
Conventional inbred mouse Mouse fails to recapitulate Murine E-cadherin is not a receptor for internalin A, so the first step of the human pathograph does not occur in this host.
Humanised E-cadherin knock-in mouse Mouse recapitulates Expression of human E-cadherin restores internalin-mediated invasion of enterocytes and crossing of the intestinal barrier.
Guinea pig Guinea pig recapitulates Internalin mediates enterocyte invasion and crossing of the intestinal barrier in the guinea pig as it does in the human gut.
Downstream
Listeriolysin O Escape from the Phagosome Internalisation puts the bacterium in a vacuole, which is the compartment the next step escapes from.
Show evidence (1 reference)
PMID:39458411 SUPPORT In Vitro
"One key group of virulence factors are internalins (Inl, with InlA and InlB being the most known), which are surface proteins that mediate bacterial adherence and the invasion of host cells. These proteins interact with specific host–cell receptors, allowing LM to penetrate the intestinal..."
Names the internalins, their receptor-mediated invasion, and the barriers they breach.
Listeriolysin O Escape from the Phagosome
Listeriolysin O is a cholesterol-dependent pore-forming cytolysin. It ruptures the phagosomal membrane before the lysosome can fuse with it, and the bacterium reaches the cytosol alive. This is the step that separates Listeria from the bacteria that macrophages simply digest.
macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
symbiont-mediated disruption of host phagosome GO:0141160 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased symbiont-mediated disruption of host phagosome (GO:0141160). GO:0141160 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Cytosolic Replication and ActA-Driven Cell-to-Cell Spread Cytosolic access is the precondition for replication and for actin-based motility.
Show evidence (1 reference)
PMID:39458411 SUPPORT In Vitro
"Another pivotal virulence factor is listeriolysin O (LLO), a pore-forming toxin that facilitates the bacterium’s escape from the phagosome into the host–cell’s cytoplasm following engulfment. This cholesterol-dependent cytolysin disrupts the phagosomal membrane, enabling LM to evade lysosomal..."
Describes the toxin, the membrane it disrupts and the escape from lysosomal degradation.
Cytosolic Replication and ActA-Driven Cell-to-Cell Spread
ActA polymerises host actin at one pole of the bacterium. The comet tail drives it through the cytoplasm and into a protrusion, the neighbouring cell engulfs the protrusion, and the organism has moved house without ever entering the extracellular space. Antibody and complement never get a look at it.
symbiont-mediated actin polymerization-dependent cell-to-cell migration in host GO:0070360 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased symbiont-mediated actin polymerization-dependent cell-to-cell migration in host (GO:0070360). GO:0070360 is a biological process from the Gene Ontology. ↑ INCREASED actin filament polymerization GO:0030041 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased actin filament polymerization (GO:0030041). GO:0030041 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Haematogenous Dissemination Local spread precedes mesenteric and bloodstream dissemination when cellular immunity does not contain it.
Failure of Th1 Cellular Containment The intracellular niche is what makes containment depend on T cell immunity rather than on antibody.
Show evidence (2 references)
PMID:39458411 SUPPORT In Vitro
"The actin assembly-inducing protein (ActA) plays a critical role in the intracellular motility of LM. Upon entry into the host–cell cytoplasm, LM hijacks the host’s actin cytoskeleton to facilitate its movement through a mechanism known as actin-based motility. ActA is essential in this process..."
Describes the actin-based motility mechanism this node names.
PMID:39458411 SUPPORT In Vitro
"Additionally, LM has evolved a sophisticated mechanism for direct cell-to-cell dissemination, allowing it to transition between host cells without exposure to the extracellular environment, further circumventing immune detection"
States the immune consequence of spreading cell to cell, which is why this node matters clinically.
Failure of Th1 Cellular Containment
Th1 CD4 cells producing interferon gamma, and the cytotoxic CD8 cells they license, are what kill infected cells. Pregnancy shifts the immune profile towards Th2, and the shift is why pregnancy is a risk factor for an organism that hides inside cells. Age, immunosuppression, malignancy and cirrhosis work on the same limb.
type II interferon-mediated signaling pathway GO:0060333 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased type II interferon-mediated signaling pathway (GO:0060333). GO:0060333 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Haematogenous Dissemination When cellular containment fails the organism reaches the bloodstream.
Show evidence (1 reference)
PMID:39458411 SUPPORT In Vitro
"The adaptive response to Listeria involves Th1-type CD4+ T cells, which produce IFN-γ and activate cytotoxic CD8+ T cells. These cells are critical for recognizing and killing infected host cells. However, the shift toward a Th2-dominant immune profile during pregnancy can reduce the efficiency..."
States the Th1 mechanism of control and the pregnancy-associated Th2 shift that weakens it.
Haematogenous Dissemination
Bacteraemia. From the blood the organism reaches two places that matter more than the rest: the central nervous system and, in pregnancy, the placenta. Both crossings use the same internalin machinery that got it through the gut.
Downstream
Central Nervous System Invasion Crossing the blood-brain barrier produces meningitis, meningoencephalitis or rhombencephalitis.
Placental Infection and Fetal Compromise Crossing the placenta infects the fetus.
Sepsis Bacteraemia is the clinical manifestation of this node in the patient.
Fever The systemic inflammatory response to bloodstream infection. Fever is the dominant manifestation of invasive disease and is often the only sign in pregnancy.
Vomiting Invasive non-neonatal listeriosis can include vomiting.
Abdominal Pain Invasive non-neonatal listeriosis can include abdominal pain.
Show evidence (1 reference)
PMID:36475874 SUPPORT Human Clinical
"Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal sepsis."
Names bacteraemia and the two invasive destinations that this node branches to.
Central Nervous System Invasion
Neurolisteriosis. Meningitis and meningoencephalitis are the usual forms, and brainstem rhombencephalitis is the one that is nearly specific to this organism. In a 71-patient cohort neurolisteriosis carried a higher fatality than bacteraemia alone, and central nervous system involvement was itself an independent fatality risk factor.
Downstream
Meningitis Invasion of the meninges is what meningitis is.
Meningoencephalitis Extension into the parenchyma, including the brainstem rhombencephalitis that is close to specific for this organism.
Headache Meningeal irritation produces headache and neck stiffness.
Reduced Consciousness Parenchymal involvement and raised intracranial pressure depress the level of consciousness.
Seizure Cortical irritation from encephalitis, cerebral oedema or infarction provokes convulsions.
Show evidence (3 references)
PMID:36475874 SUPPORT Human Clinical
"Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal sepsis."
Names meningitis and meningoencephalitis as principal presentations of the invasive disease.
PMID:38733495 SUPPORT Human Clinical
"Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%)."
Quantifies the fatality difference this node's description asserts, in the 71-patient cohort the description refers to.
PMID:38733495 SUPPORT Human Clinical
"The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects."
Identifies central nervous system involvement as an independent fatality risk factor by logistic regression, which is why this node is the one that changes prognosis.
Placental Infection and Fetal Compromise
The organism reaches the placenta, replicates there, and the inflammatory response that follows disturbs the tolerance a pregnancy depends on. Miscarriage, stillbirth, preterm labour and neonatal sepsis or meningitis follow. Hypervirulent clonal complexes 1, 4 and 6 are over-represented in these infections.
cytotrophoblast CL:0000523 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves cytotrophoblast, annotated with mononuclear cytotrophoblast cell (CL:0000523). CL:0000523 is a cell type from the Cell Ontology. syncytiotrophoblast CL:0000525 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves syncytiotrophoblast, annotated with syncytiotrophoblast cell (CL:0000525). CL:0000525 is a cell type from the Cell Ontology.
Animal models
Humanised E-cadherin knock-in mouse Mouse partially recapitulates With the humanised receptor in place the model reproduces targeting and crossing of the placental barrier, and shows internalin A and internalin B are required together.
Downstream
Fetal Distress Placental colonisation provokes a neutrophilic inflammatory response that disrupts fetal tolerance.
Premature Birth The same inflammatory response precipitates preterm labour.
Show evidence (3 references)
PMID:39458411 SUPPORT Human Clinical
"LM typically transmits from the mother to the fetus through the placenta, with transmission most commonly occurring during the third trimester when the placenta is more susceptible to infection."
States the placental route and its timing.
PMID:39458411 SUPPORT In Vitro
"Syncytiotrophoblast cells are resistant to LM adhesion on their surface, whereas cytotrophoblast cells remain susceptible"
Distinguishes the two trophoblast populations bound on this node. The organism does not enter through the surface layer that faces maternal blood, which is why both cell types are recorded rather than the generic parent.
PMID:32363991 SUPPORT Human Clinical
"Strains belonging to clonal complexes 1, 4 and 6, referred to as hypervirulent, are the most associated to maternal-neonatal infections."
Records the bacterial-genotype association with this branch. It is a pathogen-level association, not a host marker.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Listeriosis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

11
Digestive 1
Vomiting OCCASIONAL HP:0002013 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vomiting (HP:0002013). HP:0002013 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38733495 SUPPORT Human Clinical
"The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%)."
Gives the 17% figure, which supports the phenotype and the OCCASIONAL band.
Immune 3
Meningitis HP:0001287 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Meningitis (HP:0001287). HP:0001287 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36475874 SUPPORT Human Clinical
"Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal sepsis."
Names meningitis as one of the most frequent clinical presentations.
Meningoencephalitis Infectious encephalitis HP:0002383 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Infectious encephalitis (HP:0002383). HP:0002383 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36475874 SUPPORT Human Clinical
"Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal sepsis."
Names meningoencephalitis alongside meningitis as a principal presentation.
Sepsis HP:0100806 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sepsis (HP:0100806). HP:0100806 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36475874 SUPPORT Human Clinical
"Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal sepsis."
Names bacteraemia first among the presentations of listerial disease.
Metabolism 1
Fever VERY_FREQUENT HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38733495 SUPPORT Human Clinical
"The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%)."
Gives the 88% figure that supports both the phenotype and the VERY_FREQUENT band in this cohort.
Nervous System 3
Headache FREQUENT HP:0002315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Headache (HP:0002315). HP:0002315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38733495 SUPPORT Human Clinical
"The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%)."
Gives the 32% figure, which supports the phenotype and the FREQUENT band.
Reduced Consciousness OCCASIONAL HP:0004372 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Reduced consciousness (HP:0004372). HP:0004372 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38733495 SUPPORT Human Clinical
"The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%)."
Gives the 25% figure, which supports the phenotype and the OCCASIONAL band.
Seizure OCCASIONAL HP:0001250 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Seizure (HP:0001250). HP:0001250 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38733495 SUPPORT Human Clinical
"The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%)."
Gives the 8% figure, which supports the phenotype and the OCCASIONAL band.
Prenatal and Birth 2
Fetal Distress FREQUENT HP:0025116 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fetal distress (HP:0025116). HP:0025116 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38733495 SUPPORT Human Clinical
"The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%)."
Gives the 75% figure that supports both the phenotype and the FREQUENT band.
Premature Birth FREQUENT HP:0001622 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Premature birth (HP:0001622). HP:0001622 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38733495 SUPPORT Human Clinical
"The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%)."
Gives the 50% preterm figure among neonatal cases, which supports the phenotype and the FREQUENT band.
Constitutional 1
Abdominal Pain OCCASIONAL HP:0002027 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abdominal pain (HP:0002027). HP:0002027 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38733495 SUPPORT Human Clinical
"The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%)."
Gives the 12% figure, which supports the phenotype and the OCCASIONAL band.
💊

Medical Actions

3
Ampicillin or Amoxicillin
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: ampicillin CHEBI:28971 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ampicillin (CHEBI:28971). CHEBI:28971 is a therapeutic agent from Chemical Entities of Biological Interest. amoxicillin CHEBI:2676 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses amoxicillin (CHEBI:2676). CHEBI:2676 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
The first-line therapy, at high dose and intravenously for invasive disease. These agents block peptidoglycan cross-linking. The clinically important negative is that cephalosporins do not work against this organism, which is why empirical meningitis regimens add ampicillin whenever Listeria is plausible.
Mechanism Target:
INHIBITS Cytosolic Replication and ActA-Driven Cell-to-Cell Spread — Blocking cell wall synthesis kills replicating organisms and so ends the intracellular expansion this node describes.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"In the treatment of listeriosis, β-lactam antibiotics are considered the first-line therapy. Ampicillin and amoxicillin are the preferred agents for treating listeriosis during pregnancy. These antibiotics inhibit bacterial cell wall synthesis by blocking peptidoglycan cross-linking, which is..."
States the drug class, its molecular target and that viability depends on it.
Show evidence (2 references)
PMID:39458411 SUPPORT Human Clinical
"In the treatment of listeriosis, β-lactam antibiotics are considered the first-line therapy. Ampicillin and amoxicillin are the preferred agents for treating listeriosis during pregnancy. These antibiotics inhibit bacterial cell wall synthesis by blocking peptidoglycan cross-linking, which is..."
Establishes the first-line status and the mechanism of the agents named here.
PMID:39458411 SUPPORT Human Clinical
"Additionally, several classes of antibiotics, including cephalosporins, clindamycin, and chloramphenicol, are known to be ineffective against LM."
Records the negative that matters at the bedside. Cephalosporin-based empirical cover misses this organism.
Gentamicin
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: gentamicin CHEBI:17833 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses gentamicin, annotated with gentamycin (CHEBI:17833). CHEBI:17833 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
An aminoglycoside added to the beta-lactam in severe disease, for synergy. The incremental benefit is not established and it carries nephrotoxicity and ototoxicity, so its use is selective.
Mechanism Target:
INHIBITS Cytosolic Replication and ActA-Driven Cell-to-Cell Spread — The aminoglycoside is added to the beta-lactam for a synergistic bactericidal effect on the replicating organism, so it acts on the same node ampicillin does.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"In cases of severe maternal infection, the addition of an aminoglycoside, such as gentamicin, is advised due to its synergistic bactericidal effect."
States the indication and the synergistic bactericidal effect this edge asserts.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"Early diagnosis and treatment with antibiotics, such as ampicillin or gentamicin, are crucial for maternal and neonatal outcomes."
Names gentamicin alongside ampicillin as the antibiotic treatment for maternal and neonatal disease.
Trimethoprim-Sulfamethoxazole
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: trimethoprim CHEBI:45924 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses trimethoprim (CHEBI:45924). CHEBI:45924 is a therapeutic agent from Chemical Entities of Biological Interest. sulfamethoxazole CHEBI:9332 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses sulfamethoxazole (CHEBI:9332). CHEBI:9332 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
The alternative for patients who cannot take a beta-lactam. Both curated first-line options are beta-lactams, so penicillin allergy leaves this regimen and erythromycin as the route. Trimethoprim is a folate antagonist, which is why the combination is used with caution in the first trimester.
Mechanism Target:
INHIBITS Cytosolic Replication and ActA-Driven Cell-to-Cell Spread — Sequential blockade of bacterial tetrahydrofolate synthesis halts replication of the intracellular organism.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"For patients with a penicillin allergy, alternative treatments include trimethoprim/sulfamethoxazole or erythromycin"
Establishes the regimen as the substitute when the beta-lactam that acts on this node cannot be given.
Show evidence (2 references)
PMID:39458411 SUPPORT Human Clinical
"For patients with a penicillin allergy, alternative treatments include trimethoprim/sulfamethoxazole or erythromycin"
Names the regimen as an alternative for penicillin-allergic patients.
PMID:39458411 SUPPORT Human Clinical
"The combination of trimethoprim/sulfamethoxazole may also be utilized, available in both oral and intravenous forms; however, its use during pregnancy poses potential risks, particularly due to trimethoprim’s folate antagonism, which may adversely affect fetal development, especially in the..."
Records the folate-antagonism caution in pregnancy that qualifies this option.
🌍

Environmental Factors

1
Ingestion of contaminated ready-to-eat food
exposure to processed meat food product via ingestion ECTO:0070084 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is exposure to processed meat food product via ingestion (ECTO:0070084). ECTO:0070084 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
The exposure that starts the disease. Deli meats, unpasteurised soft cheese, smoked fish, prepared salads. ECTO has no term for an unpasteurised-dairy or ready-to-eat-food exposure, so the processed-meat term is used as the closest available binding for one arm of the route.
Show evidence (1 reference)
PMID:36475874 SUPPORT Human Clinical
"Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can cause severe invasive infections upon ingestion with contaminated food."
States that invasive infection follows ingestion of contaminated food, which is the exposure this entry records.
Mechanism Target:
TRIGGERS Intestinal Epithelial Invasion by Internalins — Ingestion delivers viable organisms to the intestinal epithelium, where invasion begins.
Show evidence (1 reference)
PMID:39458411 SUPPORT In Vitro
"One key group of virulence factors are internalins (Inl, with InlA and InlB being the most known), which are surface proteins that mediate bacterial adherence and the invasion of host cells. These proteins interact with specific host–cell receptors, allowing LM to penetrate the intestinal..."
Places the internalin-mediated penetration of the intestinal epithelium immediately downstream of the ingested organism.
🔬

Diagnosis

4
Blood Culture (Positive for Listeria monocytogenes)
The gold standard for non-pregnancy-associated invasive disease. Direct microscopy is impractical because the bacterial load in blood and cerebrospinal fluid is low.
microbial culture procedure NCIT:C25300 NCI Thesaurus (NCIT)
The laboratory should be told that Listeria is suspected. The organism resembles a diphtheroid on Gram stain and is discarded as a contaminant when it is not expected.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"While the direct visualization of LM through microscopy is theoretically possible, the low bacterial load both in the blood and cerebrospinal fluid make this approach uncommon, and blood cultures remain the gold standard"
States that blood culture is the reference standard and why microscopy is not used.
Cerebrospinal Fluid Culture (Positive for Listeria monocytogenes)
Culture of cerebrospinal fluid confirms neurolisteriosis. It is obtained alongside blood culture when meningitis or meningoencephalitis is suspected.
microbial culture procedure NCIT:C25300 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"The diagnosis of listeriosis is typically confirmed through the analysis of blood or cerebrospinal fluid, where LM can be cultured and identified."
Names cerebrospinal fluid alongside blood as the specimen from which the organism is cultured.
Time to Culture Positivity
The delay is the clinical problem. Invasive listeriosis can progress inside the window in which the culture is still incubating, which is the argument for empirical cover before the result returns.
Results: Approximately 36 hours to grow sufficiently for detection
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"The bacterium usually requires approximately 36 h to grow sufficiently for detection."
Gives the time to detection this record reports.
Placental Culture (Positive for Listeria monocytogenes)
The gold standard for maternal-fetal disease, more sensitive than maternal blood culture at 80% against 55%. Placental biopsy is more specific still and permits histology showing microabscesses and chorioamnionitis.
microbial culture procedure NCIT:C25300 NCI Thesaurus (NCIT)
Performed after delivery rather than during pregnancy, because of the risk to mother and fetus.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"Placental cultures are considered the gold standard for diagnosing maternal-fetal listeriosis, offering greater sensitivity than maternal blood cultures (80% vs. 55%)."
States the reference standard for the maternal-fetal form and the sensitivity comparison this record reports.
📊

Prevalence

3
Worldwide
Annual Incidence 0.1–1.5 per 100,000 per year
Maternal and non-maternal cases together. Reported as 0.1 to 1.5 cases per 100,000 people per year.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"Globally, the incidence of listeriosis, encompassing both maternal and non-maternal cases, is estimated to range from 0.1 to 1.5 cases per 100,000 individuals annually."
States the global annual incidence range recorded here.
United States, neonates
Annual Incidence 3.0–6.0 per 100,000 live births
Neonatal listeriosis only. Reported as 3 to 6 cases per 100,000 live births.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"In the United States, the estimated incidence of neonatal listeriosis is approximately 3 to 6 cases per 100,000 live births, whereas in Europe, this rate is estimated at 2 to 8 cases per 100,000 live births"
Gives the United States neonatal figure in the same sentence as the European one.
Europe, neonates
Annual Incidence 2.0–8.0 per 100,000 live births
Neonatal listeriosis only. Reported as 2 to 8 cases per 100,000 live births.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"In the United States, the estimated incidence of neonatal listeriosis is approximately 3 to 6 cases per 100,000 live births, whereas in Europe, this rate is estimated at 2 to 8 cases per 100,000 live births"
Gives the European neonatal figure from the same sentence.
🦠

Infectious Agent

1
Listeria monocytogenes
A Gram-positive, non-spore-forming, facultatively intracellular bacillus. It grows at refrigeration temperature, tolerates acid and salt, and forms biofilms in food-processing plant, which is why ready-to-eat refrigerated food is the vehicle.
Listeria monocytogenes NCBITaxon:1639 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:36475874 SUPPORT Human Clinical
"Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can cause severe invasive infections upon ingestion with contaminated food."
Names the organism, its intracellular lifestyle and its route of entry.
↔️

Transmission

2
Foodborne ingestion
Ingestion of contaminated ready-to-eat food. Refrigerated foods eaten without reheating are the classic vehicle.
Show evidence (1 reference)
PMID:36475874 SUPPORT Human Clinical
"Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can cause severe invasive infections upon ingestion with contaminated food."
States ingestion of contaminated food as the route by which invasive infection is acquired.
Vertical transplacental transmission
Mother to fetus across the placenta, most often in the third trimester.
Show evidence (1 reference)
PMID:39458411 SUPPORT Human Clinical
"LM typically transmits from the mother to the fetus through the placenta, with transmission most commonly occurring during the third trimester when the placenta is more susceptible to infection."
States the route and the trimester in which it usually happens.
⚖️

Clinical Burden

High
A rare infection with a case fatality that is high for a foodborne disease. In a 71-patient hospital cohort the fatality rate was 17% in non-neonatal and 42% in neonatal cases, neurolisteriosis killed 36% against 12% for bacteraemia alone, and central nervous system involvement was an independent fatality risk factor. Neonatal disease carries a reported 20 to 30% mortality, and the disseminated granulomatous form reaches 80% in preterm infants.
Show evidence (3 references)
PMID:38733495 SUPPORT Human Clinical
"The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%)."
Gives both case fatality rates from the cohort this rationale cites.
PMID:38733495 SUPPORT Human Clinical
"Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%)."
Gives the fatality difference between the two invasive syndromes.
PMID:39458411 SUPPORT Human Clinical
"Although neonatal listeriosis is rare, it is a potentially severe condition with a high mortality rate, ranging from 20 to 30%"
Gives the neonatal mortality range from a second source.
📊

Related Datasets

2
Listeria infection of Caco-2 cells geo:GSE3567
human MICROARRAY n=39
PMID:12537547
Human intestinal epithelial cells infected with L. monocytogenes. Relevant to the intestinal-invasion node. Found through just discover-datasets and triaged as DIRECT by title, then verified against the linked publication.
Show evidence (1 reference)
PMID:12537547 SUPPORT In Vitro
"We have examined the transcriptional response of cultured human intestinal epithelial cells to infection by L. monocytogenes, which replicates in the host cell cytoplasm and spreads from cell to cell using a form of actin-based motility."
The linked publication states what was measured in this dataset and in which cells.
Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response to Listeria infection geo:GSE225516
human BULK RNA SEQ n=18
PMID:37941135
Host transcriptional response to a pore-forming toxin, the class listeriolysin O belongs to. Relevant to the phagosome-escape node. Triaged as DIRECT by title.
Show evidence (1 reference)
PMID:37941135 SUPPORT In Vitro
"To gain isoform-level resolution of these modes of regulation, we combined long- and short-read transcriptomic analyses of the response of intestinal epithelial cells to infection by the foodborne pathogen Listeria monocytogenes."
The linked publication states the assay and the host cells this dataset comes from.
🐁

Animal Models

3
Conventional inbred mouse
Murine E-cadherin carries a glutamate where human E-cadherin carries proline at residue 16, and internalin A does not bind it. Systemic infection, hepatic and splenic colonisation and the T cell response are modelled well, so the mouse remains the standard host for immunology and for bacterial mutants. Oral, internalin-dependent invasion is not modelled.
Species
Mouse
Genotype
Wild-type (endogenous murine E-cadherin)
Publication
PMID:10406800
Pathograph links
Intestinal Epithelial Invasion by Internalins fails to recapitulate fidelity: low Murine E-cadherin is not a receptor for internalin A, so the first step of the human pathograph does not occur in this host.
Limitations: A single residue, position 16 of E-cadherin, decides the interaction. Mouse and rat carry the non-permissive residue and the authors call both inappropriate for studying all aspects of human listeriosis. A negative oral-invasion result in a conventional mouse is a property of the host receptor and says nothing about the bacterium.
Show evidence (2 references)
PMID:10406800 SUPPORT In Vitro
"Here we show that mouse E-cadherin, although very similar to human E-cadherin (85% identity), is not a receptor for internalin."
States directly that mouse E-cadherin is not a receptor for internalin, which is the failure this link records.
+ 1 more reference
Show evidence (1 reference)
PMID:10406800 SUPPORT In Vitro
"mouse, albeit previously widely used, and rat appear as inappropriate animal models to study all aspects of human listeriosis, as opposed to guinea-pig, which now stands as a small animal of choice for future in vivo studies."
The authors state the consequence for model choice, which is why this model is recorded as failing rather than omitted.
Humanised E-cadherin knock-in mouse
A knock-in line expressing humanised E-cadherin restores the internalin A receptor and with it internalin-dependent crossing of the intestinal barrier. It was built together with the gerbil, a natural host, to separate the roles of internalin A and internalin B in fetoplacental infection.
Species
Mouse
Genotype
Knock-in, ubiquitously expressing humanized E-cadherin
Publication
PMID:18806773
Pathograph links
Intestinal Epithelial Invasion by Internalins recapitulates fidelity: high Expression of human E-cadherin restores internalin-mediated invasion of enterocytes and crossing of the intestinal barrier.
Limitations: The knock-in replaces the internalin A receptor only. Other interspecies differences in placental architecture and in immunity are unchanged.
Show evidence (1 reference)
PMID:11387478 SUPPORT Model Organism
"In guinea pigs and transgenic mice expressing human E-cadherin, internalin was found to mediate invasion of enterocytes and crossing of the intestinal barrier."
Reports that internalin mediates enterocyte invasion and barrier crossing once human E-cadherin is expressed.
Placental Infection and Fetal Compromise partially recapitulates fidelity: moderate With the humanised receptor in place the model reproduces targeting and crossing of the placental barrier, and shows internalin A and internalin B are required together.
Limitations: Murine and human placentation differ in structure beyond the E-cadherin receptor, and the study pairs the knock-in with the gerbil rather than relying on either host alone.
Show evidence (1 reference)
PMID:18806773 SUPPORT Model Organism
"Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier."
States what the two models jointly establish about placental crossing, which is the facet this link claims.
Show evidence (1 reference)
PMID:18806773 SUPPORT Model Organism
"Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized E-cadherin."
Describes the knock-in line this entry records.
Guinea pig
Guinea pig E-cadherin carries the permissive residue and binds internalin, so the oral route of human listeriosis can be studied in an unmodified animal.
Species
Guinea pig
Genotype
Wild-type (permissive E-cadherin residue 16)
Publication
PMID:11387478
Pathograph links
Intestinal Epithelial Invasion by Internalins recapitulates fidelity: high Internalin mediates enterocyte invasion and crossing of the intestinal barrier in the guinea pig as it does in the human gut.
Limitations: Genetic tools and reagents for the guinea pig are limited compared with the mouse, which is why the humanised knock-in was built alongside it.
Show evidence (1 reference)
PMID:11387478 SUPPORT Model Organism
"In guinea pigs and transgenic mice expressing human E-cadherin, internalin was found to mediate invasion of enterocytes and crossing of the intestinal barrier."
Names the guinea pig alongside the transgenic mouse as the host in which internalin-mediated barrier crossing was shown.
Show evidence (1 reference)
PMID:10406800 SUPPORT In Vitro
"mouse, albeit previously widely used, and rat appear as inappropriate animal models to study all aspects of human listeriosis, as opposed to guinea-pig, which now stands as a small animal of choice for future in vivo studies."
Identifies the guinea pig as the small animal of choice on the basis of its E-cadherin residue.
{ }

Source YAML

click to show 
name: Listeriosis
creation_date: '2026-09-05T17:15:00Z'
description: 'A foodborne infection by Listeria monocytogenes, a Gram-positive bacterium that grows
  in the refrigerator and lives inside host cells. Most people who eat it are never diagnosed. In
  the old, the immunosuppressed, the pregnant and the newborn it invades, and then it presents as
  bacteraemia, as meningitis or meningoencephalitis, or as maternal-fetal infection ending in miscarriage,
  stillbirth or neonatal sepsis. The mechanism is a sequence of borrowed host machinery: internalins
  to get into the cell, listeriolysin O to get out of the vacuole, ActA to move by polymerising the
  host''s own actin, and cell-to-cell spread that keeps the organism out of the extracellular space
  where antibody and complement wait. That intracellular lifestyle is also why the immunity that controls
  it is T cell mediated, and why pregnancy, which damps Th1 responses, is the risk factor it is.'
categories:
- Foodborne Bacterial Infection
- Invasive Bacterial Infection
- Intracellular Bacterial Pathogen
parents:
- bacterial infectious disease
- foodborne illness
synonyms:
- Listeria monocytogenes infection
- invasive listeriosis
- neurolisteriosis
- maternal-neonatal listeriosis
- perinatal listeriosis
has_subtypes:
- name: Early-Onset Neonatal
  display_name: Early-onset neonatal listeriosis
  description: Disease presenting within the first six days of life, acquired in utero across an
    infected placenta. It presents with respiratory distress, sepsis, pneumonia, skin lesions or
    meningitis, is common in preterm infants, and carries the greater risk of severe complications
    and death of the two neonatal forms.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Early-onset disease, occurring within the first 6 days of life, is characterized by symptoms
      such as respiratory distress, sepsis, pneumonia, skin lesions, or meningitis.
    explanation: Defines the timing and the presenting features of this subtype.
  children:
  - Granulomatosis Infantisepticum
- name: Granulomatosis Infantisepticum
  display_name: Granulomatosis infantisepticum
  description: The severe disseminated form of early-onset neonatal disease. Granulomas form
    throughout the liver, spleen, lung, kidney, brain and skin, red or blue-grey cutaneous nodules
    and papules are visible at or shortly after birth, and mortality reaches 80% in preterm infants.
    It is close to specific for this organism.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: A severe form of early-onset neonatal listeriosis is granulomatosis infantisepticum.
      This condition is characterized by the widespread formation of granulomas in various organs
      and tissues of the fetus or newborn, including the liver, spleen, lungs, kidneys, brain, and
      skin.
    explanation: Defines the subtype and the organs the granulomas occupy.
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Granulomatosis infantisepticum is associated with a high mortality rate, which can
      reach up to 80%, particularly among preterm infants.
    explanation: Gives the mortality figure that distinguishes this subtype from ordinary
      early-onset disease.
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: A hallmark of this condition is the presence of distinctive skin lesions, which may
      appear as nodules or papules that are red or blue-gray in color.
    explanation: Records the cutaneous sign by which the subtype is recognised at the bedside.
- name: Late-Onset Neonatal
  display_name: Late-onset neonatal listeriosis
  description: Disease presenting between seven and twenty-eight days after birth, more often
    acquired around delivery than in utero. It presents with lethargy, drowsiness, vomiting or
    meningitis. It is less immediately fatal than the early-onset form and carries a risk of
    long-term neurological sequelae in survivors of meningitis.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Late-onset disease typically develops between 7 and 28 days after birth, presenting with
      symptoms including lethargy, drowsiness, vomiting, or meningitis.
    explanation: Defines the timing and the presenting features of this subtype.
infectious_agent:
- name: Listeria monocytogenes
  infectious_agent_term:
    preferred_term: Listeria monocytogenes
    term:
      id: NCBITaxon:1639
      label: Listeria monocytogenes
  description: A Gram-positive, non-spore-forming, facultatively intracellular bacillus. It grows
    at refrigeration temperature, tolerates acid and salt, and forms biofilms in food-processing plant,
    which is why ready-to-eat refrigerated food is the vehicle.
  evidence:
  - reference: PMID:36475874
    reference_title: Human Listeriosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can
      cause severe invasive infections upon ingestion with contaminated food.
    explanation: Names the organism, its intracellular lifestyle and its route of entry.
transmission:
- name: Foodborne ingestion
  description: Ingestion of contaminated ready-to-eat food. Refrigerated foods eaten without reheating
    are the classic vehicle.
  evidence:
  - reference: PMID:36475874
    reference_title: Human Listeriosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can
      cause severe invasive infections upon ingestion with contaminated food.
    explanation: States ingestion of contaminated food as the route by which invasive infection is
      acquired.
- name: Vertical transplacental transmission
  description: Mother to fetus across the placenta, most often in the third trimester.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: LM typically transmits from the mother to the fetus through the placenta, with transmission
      most commonly occurring during the third trimester when the placenta is more susceptible to
      infection.
    explanation: States the route and the trimester in which it usually happens.
environmental:
- name: Ingestion of contaminated ready-to-eat food
  description: The exposure that starts the disease. Deli meats, unpasteurised soft cheese, smoked
    fish, prepared salads. ECTO has no term for an unpasteurised-dairy or ready-to-eat-food exposure,
    so the processed-meat term is used as the closest available binding for one arm of the route.
  exposure_term:
    preferred_term: exposure to processed meat food product via ingestion
    term:
      id: ECTO:0070084
      label: exposure to processed meat food product via ingestion
  effect: Establishes the intestinal inoculum from which invasion proceeds.
  evidence:
  - reference: PMID:36475874
    reference_title: Human Listeriosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can
      cause severe invasive infections upon ingestion with contaminated food.
    explanation: States that invasive infection follows ingestion of contaminated food, which is the
      exposure this entry records.
  influences_mechanisms:
  - target: Intestinal Epithelial Invasion by Internalins
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: Ingestion delivers viable organisms to the intestinal epithelium, where invasion
      begins.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: One key group of virulence factors are internalins (Inl, with InlA and InlB being the
        most known), which are surface proteins that mediate bacterial adherence and the invasion
        of host cells. These proteins interact with specific host–cell receptors, allowing LM to penetrate
        the intestinal epithelium and breach critical barriers such as the placental and blood–brain
        barriers.
      explanation: Places the internalin-mediated penetration of the intestinal epithelium immediately
        downstream of the ingested organism.
pathophysiology:
- name: Intestinal Epithelial Invasion by Internalins
  biological_scale: CELLULAR
  description: InlA and InlB are surface proteins with leucine-rich repeats that bind host receptors
    and drive the bacterium into a cell that is not a phagocyte. InlA binds E-cadherin. The same family
    of proteins later carries the organism across the placental and blood-brain barriers, which is
    why one mechanism explains three tissue tropisms.
  cell_types:
  - preferred_term: intestinal epithelial cell
    term:
      id: CL:0002563
      label: intestinal epithelial cell
  biological_processes:
  - preferred_term: symbiont entry into host cell
    modifier: INCREASED
    term:
      id: GO:0046718
      label: symbiont entry into host cell
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: One key group of virulence factors are internalins (Inl, with InlA and InlB being the
      most known), which are surface proteins that mediate bacterial adherence and the invasion of
      host cells. These proteins interact with specific host–cell receptors, allowing LM to penetrate
      the intestinal epithelium and breach critical barriers such as the placental and blood–brain
      barriers.
    explanation: Names the internalins, their receptor-mediated invasion, and the barriers they breach.
  downstream:
  - target: Listeriolysin O Escape from the Phagosome
    causal_link_type: DIRECT
    description: Internalisation puts the bacterium in a vacuole, which is the compartment the next
      step escapes from.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: Another pivotal virulence factor is listeriolysin O (LLO), a pore-forming toxin that
        facilitates the bacterium’s escape from the phagosome into the host–cell’s cytoplasm following
        engulfment. This cholesterol-dependent cytolysin disrupts the phagosomal membrane, enabling
        LM to evade lysosomal degradation by the host immune system and establish a replicative niche
        within the cytoplasm
      explanation: States that escape follows engulfment, which is the step this edge asserts.
- name: Listeriolysin O Escape from the Phagosome
  biological_scale: CELLULAR
  description: Listeriolysin O is a cholesterol-dependent pore-forming cytolysin. It ruptures the
    phagosomal membrane before the lysosome can fuse with it, and the bacterium reaches the cytosol
    alive. This is the step that separates Listeria from the bacteria that macrophages simply digest.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: symbiont-mediated disruption of host phagosome
    modifier: INCREASED
    term:
      id: GO:0141160
      label: symbiont-mediated disruption of host phagosome
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: Another pivotal virulence factor is listeriolysin O (LLO), a pore-forming toxin that
      facilitates the bacterium’s escape from the phagosome into the host–cell’s cytoplasm following
      engulfment. This cholesterol-dependent cytolysin disrupts the phagosomal membrane, enabling
      LM to evade lysosomal degradation by the host immune system and establish a replicative niche
      within the cytoplasm
    explanation: Describes the toxin, the membrane it disrupts and the escape from lysosomal degradation.
  downstream:
  - target: Cytosolic Replication and ActA-Driven Cell-to-Cell Spread
    causal_link_type: DIRECT
    description: Cytosolic access is the precondition for replication and for actin-based motility.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: The actin assembly-inducing protein (ActA) plays a critical role in the intracellular
        motility of LM. Upon entry into the host–cell cytoplasm, LM hijacks the host’s actin cytoskeleton
        to facilitate its movement through a mechanism known as actin-based motility. ActA is essential
        in this process as it catalyzes the polymerization of actin filaments at one pole of the bacterium,
        generating actin tails that propel the bacterium forward
      explanation: States that ActA acts upon entry into the cytoplasm, which is what this edge asserts.
- name: Cytosolic Replication and ActA-Driven Cell-to-Cell Spread
  biological_scale: CELLULAR
  description: ActA polymerises host actin at one pole of the bacterium. The comet tail drives it
    through the cytoplasm and into a protrusion, the neighbouring cell engulfs the protrusion, and
    the organism has moved house without ever entering the extracellular space. Antibody and complement
    never get a look at it.
  biological_processes:
  - preferred_term: symbiont-mediated actin polymerization-dependent cell-to-cell migration in host
    modifier: INCREASED
    term:
      id: GO:0070360
      label: symbiont-mediated actin polymerization-dependent cell-to-cell migration in host
  - preferred_term: actin filament polymerization
    modifier: INCREASED
    term:
      id: GO:0030041
      label: actin filament polymerization
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: The actin assembly-inducing protein (ActA) plays a critical role in the intracellular
      motility of LM. Upon entry into the host–cell cytoplasm, LM hijacks the host’s actin cytoskeleton
      to facilitate its movement through a mechanism known as actin-based motility. ActA is essential
      in this process as it catalyzes the polymerization of actin filaments at one pole of the bacterium,
      generating actin tails that propel the bacterium forward
    explanation: Describes the actin-based motility mechanism this node names.
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: Additionally, LM has evolved a sophisticated mechanism for direct cell-to-cell dissemination,
      allowing it to transition between host cells without exposure to the extracellular environment,
      further circumventing immune detection
    explanation: States the immune consequence of spreading cell to cell, which is why this node matters
      clinically.
  downstream:
  - target: Haematogenous Dissemination
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Local spread precedes mesenteric and bloodstream dissemination when cellular immunity
      does not contain it.
    evidence:
    - reference: PMID:36475874
      reference_title: Human Listeriosis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis
        or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or
        neonatal sepsis.
      explanation: Names bacteraemia as a principal presentation, which is the node this edge reaches.
  - target: Failure of Th1 Cellular Containment
    causal_link_type: DIRECT
    description: The intracellular niche is what makes containment depend on T cell immunity rather
      than on antibody.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: The adaptive response to Listeria involves Th1-type CD4+ T cells, which produce IFN-γ
        and activate cytotoxic CD8+ T cells. These cells are critical for recognizing and killing
        infected host cells. However, the shift toward a Th2-dominant immune profile during pregnancy
        can reduce the efficiency of Th1 responses, making it more challenging to fight off intracellular
        pathogens like LM
      explanation: States that the response to this organism is Th1-dependent, which follows from
        the intracellular lifestyle described upstream.
- name: Failure of Th1 Cellular Containment
  biological_scale: ORGANISM
  description: Th1 CD4 cells producing interferon gamma, and the cytotoxic CD8 cells they license,
    are what kill infected cells. Pregnancy shifts the immune profile towards Th2, and the shift is
    why pregnancy is a risk factor for an organism that hides inside cells. Age, immunosuppression,
    malignancy and cirrhosis work on the same limb.
  biological_processes:
  - preferred_term: type II interferon-mediated signaling pathway
    modifier: DECREASED
    term:
      id: GO:0060333
      label: type II interferon-mediated signaling pathway
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: The adaptive response to Listeria involves Th1-type CD4+ T cells, which produce IFN-γ
      and activate cytotoxic CD8+ T cells. These cells are critical for recognizing and killing infected
      host cells. However, the shift toward a Th2-dominant immune profile during pregnancy can reduce
      the efficiency of Th1 responses, making it more challenging to fight off intracellular pathogens
      like LM
    explanation: States the Th1 mechanism of control and the pregnancy-associated Th2 shift that weakens
      it.
  downstream:
  - target: Haematogenous Dissemination
    causal_link_type: DIRECT
    description: When cellular containment fails the organism reaches the bloodstream.
    evidence:
    - reference: PMID:36475874
      reference_title: Human Listeriosis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Invasive listeriosis is life-threatening and a main cause of foodborne illness leading
        to hospital admissions in Western countries.
      explanation: Establishes that failure of containment produces the life-threatening invasive
        form this edge points at.
- name: Haematogenous Dissemination
  biological_scale: ORGANISM
  description: 'Bacteraemia. From the blood the organism reaches two places that matter more than
    the rest: the central nervous system and, in pregnancy, the placenta. Both crossings use the same
    internalin machinery that got it through the gut.'
  evidence:
  - reference: PMID:36475874
    reference_title: Human Listeriosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis
      or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal
      sepsis.
    explanation: Names bacteraemia and the two invasive destinations that this node branches to.
  downstream:
  - target: Central Nervous System Invasion
    causal_link_type: DIRECT
    description: Crossing the blood-brain barrier produces meningitis, meningoencephalitis or rhombencephalitis.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: One key group of virulence factors are internalins (Inl, with InlA and InlB being the
        most known), which are surface proteins that mediate bacterial adherence and the invasion
        of host cells. These proteins interact with specific host–cell receptors, allowing LM to penetrate
        the intestinal epithelium and breach critical barriers such as the placental and blood–brain
        barriers.
      explanation: Names the blood-brain barrier as one of the barriers the internalins breach.
  - target: Placental Infection and Fetal Compromise
    causal_link_type: DIRECT
    description: Crossing the placenta infects the fetus.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: LM typically transmits from the mother to the fetus through the placenta, with transmission
        most commonly occurring during the third trimester when the placenta is more susceptible to
        infection.
      explanation: States the transplacental step this edge asserts.
  - target: Sepsis
    causal_link_type: DIRECT
    description: Bacteraemia is the clinical manifestation of this node in the patient.
    evidence:
    - reference: PMID:36475874
      reference_title: Human Listeriosis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis
        or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or
        neonatal sepsis.
      explanation: Names bacteraemia as the commonest presentation, which is the phenotype this edge
        reaches.
  - target: Fever
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: The systemic inflammatory response to bloodstream infection. Fever is the dominant
      manifestation of invasive disease and is often the only sign in pregnancy.
    evidence:
    - reference: PMID:38733495
      reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
        monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache
        (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions
        (8%).
      explanation: Records fever in 88% of invasive non-neonatal cases. The cohort does not resolve
        the mediators between bacteraemia and the febrile response, which is why this edge is not
        typed as direct.
  - target: Vomiting
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Invasive non-neonatal listeriosis can include vomiting.
  - target: Abdominal Pain
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Invasive non-neonatal listeriosis can include abdominal pain.
- name: Central Nervous System Invasion
  biological_scale: ORGANISM
  description: Neurolisteriosis. Meningitis and meningoencephalitis are the usual forms, and brainstem
    rhombencephalitis is the one that is nearly specific to this organism. In a 71-patient cohort
    neurolisteriosis carried a higher fatality than bacteraemia alone, and central nervous system
    involvement was itself an independent fatality risk factor.
  evidence:
  - reference: PMID:36475874
    reference_title: Human Listeriosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis
      or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal
      sepsis.
    explanation: Names meningitis and meningoencephalitis as principal presentations of the invasive
      disease.
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs.
      12%).
    explanation: Quantifies the fatality difference this node's description asserts, in the 71-patient
      cohort the description refers to.
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia,
      and hyponatremia for all enrolled subjects.
    explanation: Identifies central nervous system involvement as an independent fatality risk factor
      by logistic regression, which is why this node is the one that changes prognosis.
  downstream:
  - target: Meningitis
    causal_link_type: DIRECT
    description: Invasion of the meninges is what meningitis is.
    evidence:
    - reference: PMID:36475874
      reference_title: Human Listeriosis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis
        or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or
        neonatal sepsis.
      explanation: Names meningitis as a principal presentation of the invasive disease this node
        describes.
  - target: Meningoencephalitis
    causal_link_type: DIRECT
    description: Extension into the parenchyma, including the brainstem rhombencephalitis that is
      close to specific for this organism.
    evidence:
    - reference: PMID:36475874
      reference_title: Human Listeriosis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis
        or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or
        neonatal sepsis.
      explanation: Names meningoencephalitis alongside meningitis as a presentation of invasive disease.
  - target: Headache
    causal_link_type: DIRECT
    description: Meningeal irritation produces headache and neck stiffness.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: This form may present as meningitis, septicemia, or encephalitis, with symptoms such
        as severe headaches, neck stiffness, confusion, loss of balance, seizures, and, in some cases,
        death.
      explanation: Lists severe headache among the symptoms of the meningitic and encephalitic form
        this node describes.
  - target: Reduced Consciousness
    causal_link_type: DIRECT
    description: Parenchymal involvement and raised intracranial pressure depress the level of consciousness.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: This form may present as meningitis, septicemia, or encephalitis, with symptoms such
        as severe headaches, neck stiffness, confusion, loss of balance, seizures, and, in some cases,
        death.
      explanation: Lists confusion among the symptoms of the same form, which is the phenotype this
        edge reaches.
  - target: Seizure
    causal_link_type: DIRECT
    description: Cortical irritation from encephalitis, cerebral oedema or infarction provokes convulsions.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: This form may present as meningitis, septicemia, or encephalitis, with symptoms such
        as severe headaches, neck stiffness, confusion, loss of balance, seizures, and, in some cases,
        death.
      explanation: Lists seizures among the symptoms of the meningitic and encephalitic form.
- name: Placental Infection and Fetal Compromise
  biological_scale: ORGANISM
  description: The organism reaches the placenta, replicates there, and the inflammatory response
    that follows disturbs the tolerance a pregnancy depends on. Miscarriage, stillbirth, preterm labour
    and neonatal sepsis or meningitis follow. Hypervirulent clonal complexes 1, 4 and 6 are over-represented
    in these infections.
  cell_types:
  - preferred_term: cytotrophoblast
    term:
      id: CL:0000523
      label: mononuclear cytotrophoblast cell
  - preferred_term: syncytiotrophoblast
    term:
      id: CL:0000525
      label: syncytiotrophoblast cell
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: LM typically transmits from the mother to the fetus through the placenta, with transmission
      most commonly occurring during the third trimester when the placenta is more susceptible to
      infection.
    explanation: States the placental route and its timing.
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: Syncytiotrophoblast cells are resistant to LM adhesion on their surface, whereas cytotrophoblast
      cells remain susceptible
    explanation: Distinguishes the two trophoblast populations bound on this node. The organism does
      not enter through the surface layer that faces maternal blood, which is why both cell types
      are recorded rather than the generic parent.
  - reference: PMID:32363991
    reference_title: Maternal-neonatal listeriosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Strains belonging to clonal complexes 1, 4 and 6, referred to as hypervirulent, are the
      most associated to maternal-neonatal infections.
    explanation: Records the bacterial-genotype association with this branch. It is a pathogen-level
      association, not a host marker.
  downstream:
  - target: Fetal Distress
    causal_link_type: DIRECT
    description: Placental colonisation provokes a neutrophilic inflammatory response that disrupts
      fetal tolerance.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: While this intense response aims to eliminate the bacteria, it can inadvertently disrupt
        fetal tolerance, leading to adverse outcomes, including preterm labor, fetal distress, and,
        potentially, fetal demise
      explanation: Names fetal distress as an outcome of the placental inflammatory response this
        node describes.
  - target: Premature Birth
    causal_link_type: DIRECT
    description: The same inflammatory response precipitates preterm labour.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: While this intense response aims to eliminate the bacteria, it can inadvertently disrupt
        fetal tolerance, leading to adverse outcomes, including preterm labor, fetal distress, and,
        potentially, fetal demise
      explanation: Names preterm labour as an outcome of the same response.
phenotypes:
- category: Constitutional
  name: Fever
  frequency: VERY_FREQUENT
  description: Present in 88% of non-neonatal cases in a 71-patient hospital cohort. In pregnancy
    it may be the only maternal sign.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache
      (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions
      (8%).
    explanation: Gives the 88% figure that supports both the phenotype and the VERY_FREQUENT band
      in this cohort.
- category: Neurologic
  name: Meningitis
  diagnostic: true
  description: One of the two defining invasive syndromes. Listeria is a leading cause of bacterial
    meningitis in the elderly and the immunosuppressed.
  phenotype_term:
    preferred_term: Meningitis
    term:
      id: HP:0001287
      label: Meningitis
  evidence:
  - reference: PMID:36475874
    reference_title: Human Listeriosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis
      or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal
      sepsis.
    explanation: Names meningitis as one of the most frequent clinical presentations.
- category: Neurologic
  name: Meningoencephalitis
  description: Parenchymal involvement, including the brainstem rhombencephalitis that is close to
    pathognomonic for this organism.
  phenotype_term:
    preferred_term: Infectious encephalitis
    term:
      id: HP:0002383
      label: Infectious encephalitis
  evidence:
  - reference: PMID:36475874
    reference_title: Human Listeriosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis
      or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal
      sepsis.
    explanation: Names meningoencephalitis alongside meningitis as a principal presentation.
- category: Neurologic
  name: Headache
  frequency: FREQUENT
  description: Reported in 32% of non-neonatal cases.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache
      (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions
      (8%).
    explanation: Gives the 32% figure, which supports the phenotype and the FREQUENT band.
- category: Neurologic
  name: Reduced Consciousness
  frequency: OCCASIONAL
  description: Reported in 25% of non-neonatal cases and a marker of central nervous system involvement.
  phenotype_term:
    preferred_term: Reduced consciousness
    term:
      id: HP:0004372
      label: Reduced consciousness
  evidence:
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache
      (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions
      (8%).
    explanation: Gives the 25% figure, which supports the phenotype and the OCCASIONAL band.
- category: Neurologic
  name: Seizure
  frequency: OCCASIONAL
  description: Convulsions in 8% of non-neonatal cases.
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache
      (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions
      (8%).
    explanation: Gives the 8% figure, which supports the phenotype and the OCCASIONAL band.
- category: Hematologic
  name: Sepsis
  diagnostic: true
  description: Bacteraemia and septicaemia, the commonest invasive presentation outside pregnancy.
  phenotype_term:
    preferred_term: Sepsis
    term:
      id: HP:0100806
      label: Sepsis
  evidence:
  - reference: PMID:36475874
    reference_title: Human Listeriosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis
      or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal
      sepsis.
    explanation: Names bacteraemia first among the presentations of listerial disease.
- category: Gastrointestinal
  name: Vomiting
  frequency: OCCASIONAL
  description: Reported in 17% of non-neonatal cases. Non-invasive febrile gastroenteritis is a separate,
    self-limited presentation in the immunocompetent.
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
  evidence:
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache
      (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions
      (8%).
    explanation: Gives the 17% figure, which supports the phenotype and the OCCASIONAL band.
- category: Gastrointestinal
  name: Abdominal Pain
  frequency: OCCASIONAL
  description: Reported in 12% of non-neonatal cases in the same 71-patient cohort.
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache
      (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions
      (8%).
    explanation: Gives the 12% figure, which supports the phenotype and the OCCASIONAL band.
- category: Obstetric
  name: Fetal Distress
  frequency: FREQUENT
  description: Present in 75% of the neonatal cases in a 71-patient cohort. Fetal loss, stillbirth
    and preterm labour are the other outcomes of placental infection; HPO codes miscarriage and stillbirth
    as clinical-course modifiers rather than phenotypic abnormalities, so they are described in the
    placental pathophysiology node instead of being bound here.
  phenotype_term:
    preferred_term: Fetal distress
    term:
      id: HP:0025116
      label: Fetal distress
  evidence:
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%).
    explanation: Gives the 75% figure that supports both the phenotype and the FREQUENT band.
- category: Obstetric
  name: Premature Birth
  frequency: FREQUENT
  description: Half of the neonatal cases in a 71-patient cohort were preterm.
  phenotype_term:
    preferred_term: Premature birth
    term:
      id: HP:0001622
      label: Premature birth
  evidence:
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%).
    explanation: Gives the 50% preterm figure among neonatal cases, which supports the phenotype and
      the FREQUENT band.
prevalence:
- population: Worldwide
  measure_type: ANNUAL_INCIDENCE
  rate_denominator: POPULATION_PER_YEAR
  rate_low: 0.1
  rate_high: 1.5
  notes: Maternal and non-maternal cases together. Reported as 0.1 to 1.5 cases per 100,000 people
    per year.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Globally, the incidence of listeriosis, encompassing both maternal and non-maternal cases,
      is estimated to range from 0.1 to 1.5 cases per 100,000 individuals annually.
    explanation: States the global annual incidence range recorded here.
- population: United States, neonates
  measure_type: ANNUAL_INCIDENCE
  rate_denominator: LIVE_BIRTHS
  rate_low: 3.0
  rate_high: 6.0
  notes: Neonatal listeriosis only. Reported as 3 to 6 cases per 100,000 live births.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: In the United States, the estimated incidence of neonatal listeriosis is approximately
      3 to 6 cases per 100,000 live births, whereas in Europe, this rate is estimated at 2 to 8 cases
      per 100,000 live births
    explanation: Gives the United States neonatal figure in the same sentence as the European one.
- population: Europe, neonates
  measure_type: ANNUAL_INCIDENCE
  rate_denominator: LIVE_BIRTHS
  rate_low: 2.0
  rate_high: 8.0
  notes: Neonatal listeriosis only. Reported as 2 to 8 cases per 100,000 live births.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: In the United States, the estimated incidence of neonatal listeriosis is approximately
      3 to 6 cases per 100,000 live births, whereas in Europe, this rate is estimated at 2 to 8 cases
      per 100,000 live births
    explanation: Gives the European neonatal figure from the same sentence.
clinical_burden:
  burden_level: HIGH
  rationale: A rare infection with a case fatality that is high for a foodborne disease. In a
    71-patient hospital cohort the fatality rate was 17% in non-neonatal and 42% in neonatal cases,
    neurolisteriosis killed 36% against 12% for bacteraemia alone, and central nervous system
    involvement was an independent fatality risk factor. Neonatal disease carries a reported 20 to
    30% mortality, and the disseminated granulomatous form reaches 80% in preterm infants.
  evidence:
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs.
      17%).
    explanation: Gives both case fatality rates from the cohort this rationale cites.
  - reference: PMID:38733495
    reference_title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria
      monocytogenes Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs.
      12%).
    explanation: Gives the fatality difference between the two invasive syndromes.
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Although neonatal listeriosis is rare, it is a potentially severe condition with a high
      mortality rate, ranging from 20 to 30%
    explanation: Gives the neonatal mortality range from a second source.
treatments:
- name: Ampicillin or Amoxicillin
  therapeutic_modality: SMALL_MOLECULE
  description: The first-line therapy, at high dose and intravenously for invasive disease. These
    agents block peptidoglycan cross-linking. The clinically important negative is that cephalosporins
    do not work against this organism, which is why empirical meningitis regimens add ampicillin whenever
    Listeria is plausible.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: ampicillin
      term:
        id: CHEBI:28971
        label: ampicillin
    - preferred_term: amoxicillin
      term:
        id: CHEBI:2676
        label: amoxicillin
  target_mechanisms:
  - target: Cytosolic Replication and ActA-Driven Cell-to-Cell Spread
    treatment_effect: INHIBITS
    description: Blocking cell wall synthesis kills replicating organisms and so ends the intracellular
      expansion this node describes.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: In the treatment of listeriosis, β-lactam antibiotics are considered the first-line
        therapy. Ampicillin and amoxicillin are the preferred agents for treating listeriosis during
        pregnancy. These antibiotics inhibit bacterial cell wall synthesis by blocking peptidoglycan
        cross-linking, which is crucial for bacterial viability.
      explanation: States the drug class, its molecular target and that viability depends on it.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: In the treatment of listeriosis, β-lactam antibiotics are considered the first-line therapy.
      Ampicillin and amoxicillin are the preferred agents for treating listeriosis during pregnancy.
      These antibiotics inhibit bacterial cell wall synthesis by blocking peptidoglycan cross-linking,
      which is crucial for bacterial viability.
    explanation: Establishes the first-line status and the mechanism of the agents named here.
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Additionally, several classes of antibiotics, including cephalosporins, clindamycin,
      and chloramphenicol, are known to be ineffective against LM.
    explanation: Records the negative that matters at the bedside. Cephalosporin-based empirical cover
      misses this organism.
- name: Gentamicin
  therapeutic_modality: SMALL_MOLECULE
  description: An aminoglycoside added to the beta-lactam in severe disease, for synergy. The incremental
    benefit is not established and it carries nephrotoxicity and ototoxicity, so its use is selective.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: gentamicin
      term:
        id: CHEBI:17833
        label: gentamycin
  target_mechanisms:
  - target: Cytosolic Replication and ActA-Driven Cell-to-Cell Spread
    treatment_effect: INHIBITS
    description: The aminoglycoside is added to the beta-lactam for a synergistic bactericidal effect
      on the replicating organism, so it acts on the same node ampicillin does.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: In cases of severe maternal infection, the addition of an aminoglycoside, such as gentamicin,
        is advised due to its synergistic bactericidal effect.
      explanation: States the indication and the synergistic bactericidal effect this edge asserts.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Early diagnosis and treatment with antibiotics, such as ampicillin or gentamicin, are
      crucial for maternal and neonatal outcomes.
    explanation: Names gentamicin alongside ampicillin as the antibiotic treatment for maternal and
      neonatal disease.
- name: Trimethoprim-Sulfamethoxazole
  therapeutic_modality: SMALL_MOLECULE
  description: The alternative for patients who cannot take a beta-lactam. Both curated first-line
    options are beta-lactams, so penicillin allergy leaves this regimen and erythromycin as the
    route. Trimethoprim is a folate antagonist, which is why the combination is used with caution in
    the first trimester.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: trimethoprim
      term:
        id: CHEBI:45924
        label: trimethoprim
    - preferred_term: sulfamethoxazole
      term:
        id: CHEBI:9332
        label: sulfamethoxazole
  target_mechanisms:
  - target: Cytosolic Replication and ActA-Driven Cell-to-Cell Spread
    treatment_effect: INHIBITS
    description: Sequential blockade of bacterial tetrahydrofolate synthesis halts replication of
      the intracellular organism.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: For patients with a penicillin allergy, alternative treatments include trimethoprim/sulfamethoxazole
        or erythromycin
      explanation: Establishes the regimen as the substitute when the beta-lactam that acts on this
        node cannot be given.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: For patients with a penicillin allergy, alternative treatments include trimethoprim/sulfamethoxazole
      or erythromycin
    explanation: Names the regimen as an alternative for penicillin-allergic patients.
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The combination of trimethoprim/sulfamethoxazole may also be utilized, available in both
      oral and intravenous forms; however, its use during pregnancy poses potential risks, particularly
      due to trimethoprim’s folate antagonism, which may adversely affect fetal development, especially
      in the first trimester.
    explanation: Records the folate-antagonism caution in pregnancy that qualifies this option.
diagnosis:
- name: Blood Culture
  presence: Positive for Listeria monocytogenes
  description: The gold standard for non-pregnancy-associated invasive disease. Direct microscopy is
    impractical because the bacterial load in blood and cerebrospinal fluid is low.
  diagnosis_term:
    preferred_term: microbial culture procedure
    term:
      id: NCIT:C25300
      label: Microbial Culture Procedure
  notes: The laboratory should be told that Listeria is suspected. The organism resembles a
    diphtheroid on Gram stain and is discarded as a contaminant when it is not expected.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: While the direct visualization of LM through microscopy is theoretically possible, the
      low bacterial load both in the blood and cerebrospinal fluid make this approach uncommon, and
      blood cultures remain the gold standard
    explanation: States that blood culture is the reference standard and why microscopy is not used.
- name: Cerebrospinal Fluid Culture
  presence: Positive for Listeria monocytogenes
  description: Culture of cerebrospinal fluid confirms neurolisteriosis. It is obtained alongside
    blood culture when meningitis or meningoencephalitis is suspected.
  diagnosis_term:
    preferred_term: microbial culture procedure
    term:
      id: NCIT:C25300
      label: Microbial Culture Procedure
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The diagnosis of listeriosis is typically confirmed through the analysis of blood or
      cerebrospinal fluid, where LM can be cultured and identified.
    explanation: Names cerebrospinal fluid alongside blood as the specimen from which the organism
      is cultured.
- name: Time to Culture Positivity
  results: Approximately 36 hours to grow sufficiently for detection
  description: The delay is the clinical problem. Invasive listeriosis can progress inside the
    window in which the culture is still incubating, which is the argument for empirical cover
    before the result returns.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The bacterium usually requires approximately 36 h to grow sufficiently for detection.
    explanation: Gives the time to detection this record reports.
- name: Placental Culture
  presence: Positive for Listeria monocytogenes
  description: The gold standard for maternal-fetal disease, more sensitive than maternal blood
    culture at 80% against 55%. Placental biopsy is more specific still and permits histology
    showing microabscesses and chorioamnionitis.
  diagnosis_term:
    preferred_term: microbial culture procedure
    term:
      id: NCIT:C25300
      label: Microbial Culture Procedure
  notes: Performed after delivery rather than during pregnancy, because of the risk to mother and
    fetus.
  evidence:
  - reference: PMID:39458411
    reference_title: Listeria in Pregnancy-The Forgotten Culprit.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Placental cultures are considered the gold standard for diagnosing maternal-fetal listeriosis,
      offering greater sensitivity than maternal blood cultures (80% vs. 55%).
    explanation: States the reference standard for the maternal-fetal form and the sensitivity
      comparison this record reports.
datasets:
- accession: geo:GSE3567
  title: Listeria infection of Caco-2 cells
  data_type: MICROARRAY
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 39
  publication: PMID:12537547
  notes: Human intestinal epithelial cells infected with L. monocytogenes. Relevant to the intestinal-invasion
    node. Found through just discover-datasets and triaged as DIRECT by title, then verified against
    the linked publication.
  evidence:
  - reference: PMID:12537547
    reference_title: A gene-expression program reflecting the innate immune response of cultured intestinal
      epithelial cells to infection by Listeria monocytogenes.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: We have examined the transcriptional response of cultured human intestinal epithelial
      cells to infection by L. monocytogenes, which replicates in the host cell cytoplasm and spreads
      from cell to cell using a form of actin-based motility.
    explanation: The linked publication states what was measured in this dataset and in which cells.
- accession: geo:GSE225516
  title: Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell
    response to Listeria infection
  data_type: BULK_RNA_SEQ
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 18
  publication: PMID:37941135
  notes: Host transcriptional response to a pore-forming toxin, the class listeriolysin O belongs
    to. Relevant to the phagosome-escape node. Triaged as DIRECT by title.
  evidence:
  - reference: PMID:37941135
    reference_title: Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated
      cell response to Listeria infection.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: To gain isoform-level resolution of these modes of regulation, we combined long- and
      short-read transcriptomic analyses of the response of intestinal epithelial cells to infection
      by the foodborne pathogen Listeria monocytogenes.
    explanation: The linked publication states the assay and the host cells this dataset comes from.
animal_models:
- name: Conventional inbred mouse
  species: Mouse
  genotype: Wild-type (endogenous murine E-cadherin)
  publication: PMID:10406800
  description: Murine E-cadherin carries a glutamate where human E-cadherin carries proline at residue
    16, and internalin A does not bind it. Systemic infection, hepatic and splenic colonisation and the
    T cell response are modelled well, so the mouse remains the standard host for immunology and for bacterial
    mutants. Oral, internalin-dependent invasion is not modelled.
  modeled_mechanisms:
  - target: Intestinal Epithelial Invasion by Internalins
    relationship: FAILS_TO_RECAPITULATE
    fidelity: LOW
    description: Murine E-cadherin is not a receptor for internalin A, so the first step of the human
      pathograph does not occur in this host.
    limitations: A single residue, position 16 of E-cadherin, decides the interaction. Mouse and rat carry
      the non-permissive residue and the authors call both inappropriate for studying all aspects of human
      listeriosis. A negative oral-invasion result in a conventional mouse is a property of the host receptor
      and says nothing about the bacterium.
    evidence:
    - reference: PMID:10406800
      reference_title: A single amino acid in E-cadherin responsible for host specificity towards the
        human pathogen Listeria monocytogenes.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: Here we show that mouse E-cadherin, although very similar to human E-cadherin (85% identity),
        is not a receptor for internalin.
      explanation: States directly that mouse E-cadherin is not a receptor for internalin, which is the
        failure this link records.
    - reference: PMID:11387478
      reference_title: 'A transgenic model for listeriosis: role of internalin in crossing the intestinal
        barrier.'
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: Murine E-cadherin, in contrast to guinea pig E-cadherin, does not interact with internalin,
        excluding the mouse as a model for addressing internalin function in vivo.
      explanation: Repeats the exclusion in the paper that built the replacement model.
  evidence:
  - reference: PMID:10406800
    reference_title: A single amino acid in E-cadherin responsible for host specificity towards the human
      pathogen Listeria monocytogenes.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: mouse, albeit previously widely used, and rat appear as inappropriate animal models to study
      all aspects of human listeriosis, as opposed to guinea-pig, which now stands as a small animal of
      choice for future in vivo studies.
    explanation: The authors state the consequence for model choice, which is why this model is recorded
      as failing rather than omitted.
- name: Humanised E-cadherin knock-in mouse
  species: Mouse
  genotype: Knock-in, ubiquitously expressing humanized E-cadherin
  publication: PMID:18806773
  description: A knock-in line expressing humanised E-cadherin restores the internalin A receptor and
    with it internalin-dependent crossing of the intestinal barrier. It was built together with the gerbil,
    a natural host, to separate the roles of internalin A and internalin B in fetoplacental infection.
  modeled_mechanisms:
  - target: Intestinal Epithelial Invasion by Internalins
    relationship: RECAPITULATES
    fidelity: HIGH
    description: Expression of human E-cadherin restores internalin-mediated invasion of enterocytes and
      crossing of the intestinal barrier.
    limitations: The knock-in replaces the internalin A receptor only. Other interspecies differences
      in placental architecture and in immunity are unchanged.
    evidence:
    - reference: PMID:11387478
      reference_title: 'A transgenic model for listeriosis: role of internalin in crossing the intestinal
        barrier.'
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: In guinea pigs and transgenic mice expressing human E-cadherin, internalin was found to
        mediate invasion of enterocytes and crossing of the intestinal barrier.
      explanation: Reports that internalin mediates enterocyte invasion and barrier crossing once human
        E-cadherin is expressed.
  - target: Placental Infection and Fetal Compromise
    relationship: PARTIALLY_RECAPITULATES
    fidelity: MODERATE
    description: With the humanised receptor in place the model reproduces targeting and crossing of the
      placental barrier, and shows internalin A and internalin B are required together.
    limitations: Murine and human placentation differ in structure beyond the E-cadherin receptor, and
      the study pairs the knock-in with the gerbil rather than relying on either host alone.
    evidence:
    - reference: PMID:18806773
      reference_title: Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: Using these two models, we uncover the essential and interdependent roles of InlA and InlB
        in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability
        of a microbe to target and cross the placental barrier.
      explanation: States what the two models jointly establish about placental crossing, which is the
        facet this link claims.
  evidence:
  - reference: PMID:18806773
    reference_title: Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: 'Here we describe two novel and complementary animal models for human listeriosis: the gerbil,
      a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized
      E-cadherin.'
    explanation: Describes the knock-in line this entry records.
- name: Guinea pig
  species: Guinea pig
  genotype: Wild-type (permissive E-cadherin residue 16)
  publication: PMID:11387478
  description: Guinea pig E-cadherin carries the permissive residue and binds internalin, so the oral
    route of human listeriosis can be studied in an unmodified animal.
  modeled_mechanisms:
  - target: Intestinal Epithelial Invasion by Internalins
    relationship: RECAPITULATES
    fidelity: HIGH
    description: Internalin mediates enterocyte invasion and crossing of the intestinal barrier in the
      guinea pig as it does in the human gut.
    limitations: Genetic tools and reagents for the guinea pig are limited compared with the mouse, which
      is why the humanised knock-in was built alongside it.
    evidence:
    - reference: PMID:11387478
      reference_title: 'A transgenic model for listeriosis: role of internalin in crossing the intestinal
        barrier.'
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: In guinea pigs and transgenic mice expressing human E-cadherin, internalin was found to
        mediate invasion of enterocytes and crossing of the intestinal barrier.
      explanation: Names the guinea pig alongside the transgenic mouse as the host in which internalin-mediated
        barrier crossing was shown.
  evidence:
  - reference: PMID:10406800
    reference_title: A single amino acid in E-cadherin responsible for host specificity towards the human
      pathogen Listeria monocytogenes.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: mouse, albeit previously widely used, and rat appear as inappropriate animal models to study
      all aspects of human listeriosis, as opposed to guinea-pig, which now stands as a small animal of
      choice for future in vivo studies.
    explanation: Identifies the guinea pig as the small animal of choice on the basis of its E-cadherin
      residue.
discussions:
- discussion_id: murine_e_cadherin_model_mismatch
  kind: HUMAN_MODEL_MISMATCH
  status: OPEN
  prompt: Does the internalin A arm of intestinal invasion, established in guinea pigs and in mice
    carrying humanised E-cadherin, hold in the human gut, and how much of the older mouse literature
    on oral listeriosis is host-artefact?
  attaches_to:
  - pathophysiology#Intestinal Epithelial Invasion by Internalins
  - pathophysiology#Placental Infection and Fetal Compromise
  rationale: Internalin A binds human E-cadherin and does not bind the murine protein, and one
    residue of E-cadherin decides it. Decades of oral-infection work in conventional mice therefore
    cannot speak to this step, and the evidence that it operates in vivo comes from the guinea pig
    and from a knock-in mouse engineered to carry the human receptor. Both are constructions
    designed to remove the mismatch, so the human claim rests on animals chosen or built for the
    purpose rather than on direct human observation. The mismatch is mechanistically load-bearing
    here because the same internalins are asserted to carry the organism across the placental and
    blood-brain barriers, and the human evidence for those crossings is a review statement rather
    than an experiment.
  proposed_experiments:
  - experiment_id: listeriosis_inla_human_intestinal_organoid
    name: Internalin A dependent invasion in human intestinal organoids
    description: Infect human intestinal organoids and primary enterocytes with wild-type and inlA
      deletion strains, and run the same comparison in the humanised E-cadherin knock-in mouse. The
      question is whether the engineered host reproduces the human tissue, or only the human
      receptor.
    decision_criterion: The inlA deletion strain shows the same relative loss of invasion in human
      organoids as it does in the humanised knock-in mouse.
    would_support:
    - pathophysiology#Intestinal Epithelial Invasion by Internalins
    supporting_outcome:
    - Concordant inlA dependence in human tissue and in the humanised mouse would make the mouse
      result transferable to the human gut.
    refuting_outcome:
    - A human-tissue invasion phenotype that does not depend on inlA would mean the knock-in
      restores the receptor without restoring the human mechanism.
    evidence:
    - reference: PMID:11387478
      reference_title: 'A transgenic model for listeriosis: role of internalin in crossing the intestinal
        barrier.'
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: In guinea pigs and transgenic mice expressing human E-cadherin, internalin was found
        to mediate invasion of enterocytes and crossing of the intestinal barrier.
      explanation: This is the result the experiment is designed to test for transferability. It was
        obtained in two engineered or selected hosts and not in human tissue.
  - experiment_id: listeriosis_inla_placental_explant_trophoblast
    name: Trophoblast-stratified invasion in human placental explants
    description: Assay internalin binding and bacterial invasion in human placental explants,
      separating cytotrophoblast from syncytiotrophoblast, to test the reported susceptibility
      difference directly in human tissue rather than by inference from the mouse.
    decision_criterion: Invasion is measurable in cytotrophoblast and absent or markedly lower at
      the syncytiotrophoblast surface.
    would_support:
    - pathophysiology#Placental Infection and Fetal Compromise
    supporting_outcome:
    - A cytotrophoblast-restricted invasion pattern in human tissue would ground the tropism claim
      without relying on an engineered host.
    refuting_outcome:
    - Equal invasion of both populations would mean the entry's trophoblast distinction is a
      cell-culture artefact.
    evidence:
    - reference: PMID:39458411
      reference_title: Listeria in Pregnancy-The Forgotten Culprit.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: Syncytiotrophoblast cells are resistant to LM adhesion on their surface, whereas cytotrophoblast
        cells remain susceptible
      explanation: The claim this experiment would test in human placental tissue. As cited it rests
        on cultured cells rather than on explants.
  evidence:
  - reference: PMID:10406800
    reference_title: A single amino acid in E-cadherin responsible for host specificity towards the
      human pathogen Listeria monocytogenes.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: Here we show that mouse E-cadherin, although very similar to human E-cadherin (85% identity),
      is not a receptor for internalin.
    explanation: States the receptor mismatch that makes this a model-fidelity question rather than
      an evidence gap.
references:
- reference: PMID:10406800
  title: A single amino acid in E-cadherin responsible for host specificity towards the human pathogen
    Listeria monocytogenes.
- reference: PMID:11387478
  title: 'A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier.'
- reference: PMID:18806773
  title: Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis.
- reference: PMID:32363991
  title: Maternal-neonatal listeriosis.
- reference: PMID:36475874
  title: Human Listeriosis.
- reference: PMID:38733495
  title: 'Clinical Characteristics and Fatality Risk Factors for Patients with Listeria monocytogenes
    Infection: A 12-Year Hospital-Based Study in Xi''an, China.'
- reference: PMID:39458411
  title: Listeria in Pregnancy-The Forgotten Culprit.
disease_term:
  preferred_term: listeriosis
  term:
    id: MONDO:0005828
    label: listeriosis
notes: Host genetics. There is no human causal gene for listeriosis in the Mendelian sense, so the
  entry carries no genetic section. The genetic determinants that matter are bacterial (prfA, inlA/inlB,
  hly, actA, plcA/plcB, the LIPI-3 and LIPI-4 islands) and they belong to the organism, not to the
  patient. Susceptibility is immune competence interacting with exposure dose and bacterial genotype.
review_notes: ECTO was searched for an exposure term covering unpasteurised dairy or ready-to-eat
  refrigerated food and none exists. ECTO:0070084 (processed meat food product) binds one arm of the
  route and is used with that limitation stated in the entry. Dataset curation returned twelve
  candidates from just discover-datasets; the two human in-vitro studies were kept after title
  triage and the mouse candidates were left out as not directly informative for a human entry.
  Miscarriage and stillbirth are not bound as phenotypes because HPO files HP:0005268 under
  clinical course rather than phenotypic abnormality, and the PhenotypeTerm dynamic enum rejects
  it; both outcomes are described in the placental pathophysiology node instead. No genetic section
  is curated and the reason is recorded in notes. Vomiting and Abdominal Pain are deliberately left
  without an incoming causal edge. The cohort that supplies their frequencies reports them as
  manifestations of invasive disease without attributing them to a step, and the only cached
  sentence that places gastrointestinal symptoms mechanistically describes the non-invasive
  gastroenteritis form, in which the organism does not take the pathograph's invasion route. An
  edge from the intestinal-invasion node would assert a mechanism neither source states. Every
  other phenotype in the entry is reached from the chain. The three subtypes carry no
  subtype_term. MONDO holds only listeriosis (MONDO:0005828) plus two non-human-animal terms, and
  has nothing for early-onset or late-onset neonatal disease or for granulomatosis infantisepticum,
  so the test_data warning about missing subtype_term is expected rather than an oversight.
📚

References & Deep Research

References

7
PMID:10406800
A single amino acid in E-cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes.
No top-level findings curated for this source.
PMID:11387478
A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier.
No top-level findings curated for this source.
PMID:18806773
Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis.
No top-level findings curated for this source.
PMID:32363991
Maternal-neonatal listeriosis.
No top-level findings curated for this source.
PMID:36475874
Human Listeriosis.
No top-level findings curated for this source.
PMID:38733495
Clinical Characteristics and Fatality Risk Factors for Patients with Listeria monocytogenes Infection: A 12-Year Hospital-Based Study in Xi'an, China.
No top-level findings curated for this source.
PMID:39458411
Listeria in Pregnancy-The Forgotten Culprit.
No top-level findings curated for this source.

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Listeriosis · 2026-09-05T21:55:45Z · View source

New entry for listeriosis (MONDO:0005828), curated from an Edison falcon deep-research report (research/Listeriosis-deep-research-falcon.md) plus primary literature. Every snippet was extracted programmatically as an exact substring of the cached reference rather than transcribed, because the two full-text sources use en-dashes and curly apostrophes that hand-copying gets wrong. The pathograph runs ingestion, internalin-mediated intestinal epithelial invasion, listeriolysin O escape from the phagosome, cytosolic replication with ActA-driven cell-to-cell spread, failure of Th1 cellular containment, haematogenous dissemination, and then branches to CNS invasion and to placental infection with fetal compromise. The environmental entry links the food exposure into the pathograph with TRIGGERS and carries its own evidence block. Ten phenotypes, two treatments, two GEO datasets. Falcon suggested GO:0030260 for entry into host cell, GO:0046710 for phagosome escape and GO:0009405 for pathogenesis; the first does not exist, the second is GDP metabolic process and the third is obsolete, so all three were replaced with terms resolved through OAK (GO:0046718, GO:0141160, GO:0070360). HP:0005268 Miscarriage was rejected by the PhenotypeTerm dynamic enum because HPO files it under clinical course rather than phenotypic abnormality; Fetal distress HP:0025116 is bound instead and the miscarriage and stillbirth outcomes are described in the placental node. Validated with 'just validate': 37/37 snippets verified, term validation clean. check-entity-refs and check-duplicate-keys pass, 'just verify-datasets' resolves both accessions, compliance 100.0% global and weighted.

Falcon ▸
Disease Characteristics Research Template
Edison Scientific Literature 35 citations 2026-09-05T17:25:12.779139

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Listeriosis
  • MONDO ID: MONDO:0005828 (if available)
  • Category: Infectious

Research Objectives

Please provide a comprehensive research report on Listeriosis covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

Present this section as an ordered causal chain first, then the detail below. Open with a numbered sequence of mechanistic steps running from the initiating lesion (mutation, exposure, infection) to the clinical manifestation, one step per line, each naming what it causes next. State the causal verb explicitly ("leads to", "results in") and say where a step is inferred rather than demonstrated. Where the mechanism branches, show the branch. The categories below are a checklist of what to cover within those steps, not the organizing structure — a step may draw on several of them, and a category may contribute to several steps.

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest NCIT (NCI Thesaurus) clinical-intervention terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
  • Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, NCIT, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (NCIT terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Listeriosis (MONDO:0005828): comprehensive disease-characteristics report

Executive summary and evidence scope

Listeriosis is a foodborne zoonotic infection caused principally by Listeria monocytogenes, a Gram-positive, non-spore-forming, facultatively anaerobic and facultatively intracellular bacillus. Most exposure does not produce recognized invasive disease, but susceptible hosts can develop bacteremia/sepsis, meningitis or meningoencephalitis, and maternal–fetal or neonatal infection. The authoritative 2023 review’s abstract states: “Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can cause severe invasive infections upon ingestion with contaminated food.” (koopmans2023humanlisteriosis pages 1-3)

This report integrates aggregated disease-level resources, reviews, surveillance evidence, model studies, and retrospective human cohorts. It is not derived from one patient’s EHR. Patient-level observations are included only where explicitly identified as hospital cohorts. Because the retrieved literature did not consistently expose PMID metadata, DOI URLs and publication dates are supplied; PMIDs should not be inferred where unavailable.

Listeriosis Knowledge-Base Core Current knowledge Ontology suggestions Evidence type Source year / DOI
Disease identity and etiology Rare, potentially severe foodborne zoonosis caused primarily by the Gram-positive, facultatively intracellular bacterium Listeria monocytogenes, usually after ingestion of contaminated food. Principal invasive presentations are bacteremia or septicemia, meningitis or meningoencephalitis, and maternal–fetal or neonatal infection. MONDO: MONDO:0005828; NCBI Taxon: 1639 Authoritative review 2023; 10.1128/cmr.00060-19 (koopmans2023humanlisteriosis pages 1-3)
Principal phenotypes Among invasive cases, pregnancy-associated or neonatal infection accounts for approximately 14%, bacteremia or septicemia 52%, and CNS infection 31%; uncommon focal sites generally account for less than 1% each. HPO: Fever HP:0001945; Meningitis HP:0001287; Encephalitis HP:0002383; Sepsis HP:0100806; Miscarriage HP:0005268 Aggregated review evidence 2023; 10.1128/cmr.00060-19 (koopmans2023humanlisteriosis pages 1-3)
Recent phenotype frequencies In a 2024 cohort of 71 confirmed cases, non-neonatal manifestations included fever 88%, headache 32%, altered consciousness 25%, vomiting 17%, abdominal pain 12%, and convulsions 8%. Among neonates, fetal distress occurred in 75% and prematurity in 50%. HPO: Headache HP:0002315; Altered consciousness HP:0004372; Vomiting HP:0002013; Abdominal pain HP:0002027; Seizure HP:0001250; Premature birth HP:0001622 Human retrospective cohort, 2011–2023 2024; 10.1007/s40121-024-00986-3 (xu2024clinicalcharacteristicsand pages 1-2)
Major risk groups Highest-risk groups are pregnant people and fetuses or neonates, older adults, and people with impaired cell-mediated immunity or major chronic disease. Pregnancy is reported to increase susceptibility about 17-fold; gestational suppression of Th1 and IFN-gamma responses impairs intracellular clearance. HPO: Immunodeficiency HP:0002721; GO: response to bacterium GO:0009617; interferon-gamma-mediated signaling GO:0060333; CL: macrophage CL:0000235; T cell CL:0000084 Human and mechanistic review evidence 2024; 10.3390/microorganisms12102102 (kraus2024listeriainpregnancy—the pages 6-7)
Host Mendelian genetics No Mendelian host gene or pathogenic germline variant is established as the cause of listeriosis. OMIM-style causal-gene, inheritance, penetrance, carrier-frequency, chromosomal-abnormality, and somatic-variant fields are not applicable. Routine human genetic testing is not indicated. Mendelian causal-gene and ClinVar-variant fields: not applicable Evidence-gap assessment; susceptibility research is ongoing Clinical studies include NCT03357536 and NCT02924220; no validated causal variant established
Virulence chain: regulation and entry Host temperature and intracellular glutathione activate PrfA, inducing bacterial virulence genes. Bile resistance supports intestinal survival. InlA–E-cadherin and InlB–MET interactions lead to epithelial adhesion and internalization. GO: pathogenesis GO:0009405; entry into host cell GO:0030260; CL: intestinal epithelial cell CL:0002563; UBERON: intestine UBERON:0000160; CHEBI: glutathione CHEBI:16856 Mechanistic review integrating in-vitro and animal evidence 2023–2024; 10.1128/cmr.00060-19 (kraus2024listeriainpregnancy—the pages 2-4, koopmans2023humanlisteriosis pages 5-7)
Virulence chain: intracellular spread Internalization leads to phagosomal residence; listeriolysin O and phospholipases disrupt the vacuole, resulting in cytosolic escape. Cytosolic replication and ActA-mediated actin polymerization lead to intracellular motility and direct cell-to-cell spread. GO: escape from host phagosome GO:0046710; actin-filament polymerization GO:0030041; GO-CC: phagocytic vesicle GO:0045335; cytosol GO:0005829; CL: macrophage CL:0000235 Predominantly in-vitro and model-organism evidence 2024; 10.3390/microorganisms12102102 (kraus2024listeriainpregnancy—the pages 2-4, kraus2024listeriainpregnancy—the pages 1-2)
Barrier and organ disease Dissemination produces bacteremia and seeding of liver and spleen. Placental invasion may cause fetal infection, miscarriage, stillbirth, preterm birth, or neonatal sepsis; CNS invasion may cause meningitis, meningoencephalitis, rhombencephalitis, or abscess. LIPI-4 in hypervirulent CC4 is associated with maternofetal and neuromeningeal disease, although its mechanism remains unresolved. UBERON: liver UBERON:0002107; spleen UBERON:0002106; placenta UBERON:0001987; brain UBERON:0000955; meninges UBERON:0000363; CL: trophoblast cell CL:0000351; neuron CL:0000540 Human association plus model-derived mechanism 2023–2024; 10.1128/cmr.00060-19, 10.3390/microorganisms12102102 (kraus2024listeriainpregnancy—the pages 6-7, koopmans2023humanlisteriosis pages 5-7)
Diagnostics Definitive diagnosis relies primarily on blood or CSF culture; growth may take about 36 hours. In pregnancy, placental culture was reported as more sensitive than maternal blood culture, 80% versus 55%, and placental-biopsy sensitivity was reported as 100%. WGS and wgMLST support outbreak surveillance rather than host diagnosis. NCIT: Blood Culture C92225; Lumbar Puncture C15327; Whole Genome Sequencing C101295; UBERON: blood UBERON:0000178; cerebrospinal fluid UBERON:0001359; placenta UBERON:0001987 Clinical review and surveillance evidence 2023–2024; 10.1128/cmr.00060-19, 10.3390/microorganisms12102102 (kraus2024listeriainpregnancy—the pages 4-6, kraus2024listeriainpregnancy—the pages 6-7, koopmans2023humanlisteriosis pages 5-7)
First-line therapy First-line treatment is high-dose intravenous ampicillin or amoxicillin, often with short-course gentamicin for severe invasive disease. Adult neurolisteriosis generally requires 12 g/day aminopenicillin for at least 21 days; brain abscess or rhombencephalitis requires at least six weeks with imaging follow-up. Co-trimoxazole is a major beta-lactam-allergy alternative. CHEBI: ampicillin CHEBI:28971; amoxicillin CHEBI:2676; gentamicin CHEBI:27412; trimethoprim CHEBI:45924; sulfamethoxazole CHEBI:9332; NCIT: Antibiotic Therapy C15614 Expert review and guideline synthesis; randomized trials lacking 2023; 10.1128/cmr.00060-19 (koopmans2023humanlisteriosis pages 26-27)
Prognosis A 2024 cohort found fatality of 42% in neonates, 17% in non-neonates, 36% in neurolisteriosis, and 12% in bacteremic disease. CNS involvement, hyperbilirubinemia, and hyponatremia predicted fatality. A separate 63-adult cohort reported 27% in-hospital mortality, ICU admission in 44.4%, residual neurologic deficits in 23.9% of survivors, and brain abscess in 13.0%. HPO: Neurological deficit HP:0011446; Brain abscess HP:0030049; Hyponatremia HP:0002902; Hyperbilirubinemia HP:0002904; NCIT: Intensive Care C53511 Human retrospective cohorts 2024; 10.1007/s40121-024-00986-3, 10.1186/s12866-024-03478-z (xu2024clinicalcharacteristicsand pages 1-2)
Prevention No licensed human vaccine or routine asymptomatic screening exists. Prevention includes pasteurization, adequate cooking, reheating or avoiding deli meats and hot dogs, avoiding unpasteurized dairy and high-risk soft cheeses, washing produce, preventing cross-contamination, environmental sanitation, and food-chain WGS surveillance. High-pressure processing at 100–600 MPa can reduce contamination, although surviving cells may recover. NCIT: Food Safety C17577; Patient Education C16960; Whole Genome Sequencing C101295 Public-health, surveillance, and food-processing evidence 2023–2024; 10.1128/cmr.00060-19, 10.3390/foods13010014 (kraus2024listeriainpregnancy—the pages 1-2, kraus2024listeriainpregnancy—the pages 6-7, koopmans2023humanlisteriosis pages 5-7)
Veterinary relevance Natural disease principally affects cattle, sheep, and goats, producing encephalitis or meningoencephalitis, septicemia, abortion, and neonatal loss. Abortions typically occur during the final third of gestation and may affect up to 20% of animals. Ruminants act as reservoirs that contaminate food and farm environments. NCBI Taxon: cattle 9913; sheep 9940; goat 9925 Veterinary review and field evidence 2024; 10.3390/microorganisms12102055 (koncurat2024listeriosischaracteristicsoccurrence pages 1-2, koncurat2024listeriosischaracteristicsoccurrence pages 8-9)
Models and functional genomics Mouse, humanized E-cadherin mouse, gerbil, zebrafish, cultured epithelial and macrophage systems, placental explants, brain slices, and organoids model intracellular infection and barrier crossing. Standard mice incompletely model oral InlA-mediated entry because murine E-cadherin is poorly recognized. A 2024 RECON/Akr1c13-disrupted mouse Tn-seq study identified 135 bacterial fitness genes; deletion of folD reduced liver growth by 2.5 log10, while deletion of alsR caused 4-log10 liver and 3-log10 spleen attenuation. CL: macrophage CL:0000235; fibroblast CL:0000057; intestinal epithelial cell CL:0002563; trophoblast cell CL:0000351; UBERON: liver UBERON:0002107; spleen UBERON:0002106 Animal, ex-vivo, in-vitro, and genome-wide Tn-seq evidence 2020–2024; 10.1111/cmi.13186, 10.1128/mbio.01332-24

Table: A concise evidence table summarizing listeriosis identity, phenotypes, risks, pathogenesis, diagnosis, treatment, prognosis, prevention, and comparative biology. It integrates current ontology suggestions with recent human, mechanistic, veterinary, and model-system evidence.

1. Disease information

Definition and classification

L. monocytogenes is ubiquitous in soil, groundwater, animal and human feces, farms, food-processing environments, and refrigerated foods. Its psychrotolerance, acid and salt tolerance, intracellular lifestyle, and biofilm formation explain both food-chain persistence and invasive pathogenicity. It can grow at approximately 0–4°C, survive around pH 4.4–9.6, and tolerate 10–12% salt. (kraus2024listeriainpregnancy—the pages 1-2, koncurat2024listeriosischaracteristicsoccurrence pages 1-2, koopmans2023humanlisteriosis pages 1-3)

Suggested identifiers

  • MONDO: MONDO:0005828.
  • MeSH: Listeriosis.
  • ICD-10-CM: A32, with syndrome-specific children such as A32.0 cutaneous listeriosis, A32.1 listerial meningitis/meningoencephalitis, A32.7 listerial sepsis, A32.8 other forms, and A32.9 unspecified. Pregnancy and neonatal coding may additionally require obstetric/perinatal codes.
  • ICD-11: listeriosis is classified among bacterial infections; exact extension coding should be validated against the current local ICD-11 release.
  • NCBI Taxonomy: L. monocytogenes, Taxon 1639.
  • OMIM/Orphanet: not primarily applicable: this is an acquired infection rather than a Mendelian disorder. No disease-specific OMIM causal-gene entry should be assigned.

Synonyms: listerial infection, Listeria monocytogenes infection, invasive listeriosis, non-invasive listerial gastroenteritis, neurolisteriosis, maternal–fetal or perinatal listeriosis, neonatal listeriosis, and historically “circling disease” in ruminants.

Among invasive cases summarized in 2023, bacteremia/septicemia comprised about 52%, CNS infection 31%, and pregnancy-associated/neonatal infection 14%; unusual focal infections were generally each below 1%. Serotypes 4b, 1/2a, and 1/2b account for approximately 92–95% of clinical isolates. (koopmans2023humanlisteriosis pages 1-3)

2. Etiology, risk, and protective factors

Causal factor and transmission

The necessary infectious cause is viable pathogenic L. monocytogenes. Infection usually follows ingestion of contaminated ready-to-eat meats, unpasteurized dairy or soft cheeses, prepacked sandwiches, smoked fish, prepared produce, salads, or fruit. Vertical transplacental transmission causes fetal disease; intrapartum or nosocomial neonatal transmission is uncommon but documented. Direct occupational animal exposure is possible, particularly for cutaneous disease. (kraus2024listeriainpregnancy—the pages 1-2, koopmans2023humanlisteriosis pages 1-3)

Pathogen-level risk varies. Four lineages, 13 serotypes, and more than 1,500 sequence types are recognized. LIPI-4 is associated with hypervirulent CC4 and maternal–fetal/neuromeningeal disease; LIPI-3, encoding listeriolysin S, occurs in about 88% of lineage-I strains. CC1, CC2, CC4, and CC6 have been associated with adverse pregnancy outcomes, with CC4 showing notable placental tropism. These are bacterial genomic determinants—not inherited human variants. (kraus2024listeriainpregnancy—the pages 6-7, koopmans2023humanlisteriosis pages 5-7)

Human risk factors

  • Pregnancy, fetus/neonatal age, older age, impaired T-cell immunity, malignancy, transplantation, corticosteroid or other immunosuppressive therapy, cirrhosis, renal disease, diabetes, and other major chronic illness increase invasive risk.
  • Pregnancy is reported to confer approximately 17-fold higher susceptibility. The mechanistic explanation is a gestational shift away from Th1/cell-mediated immunity, with reduced IFN-γ-dependent macrophage and cytotoxic-T-cell activity against an intracellular pathogen. (kraus2024listeriainpregnancy—the pages 6-7)
  • In one 2024 adult hospital cohort, 88.9% of invasive cases had an immunocompromising condition, illustrating strong enrichment but not population-level relative risk.
  • Environmental/behavioral risks include consumption of unheated ready-to-eat foods, unpasteurized milk products, poor refrigerator and kitchen hygiene, cross-contamination, and occupational contact with infected animals or abortion products.

Genetic, epigenetic, and gene–environment considerations

No human germline mutation, chromosomal abnormality, or somatic variant is established as the cause of ordinary listeriosis. Therefore, ACMG classification, gnomAD allele frequency, penetrance, carrier frequency, inheritance, anticipation, mosaicism, and founder-effect fields are not applicable. Human susceptibility is better described as multifactorial immune competence interacting with exposure dose and bacterial genotype. Dedicated studies include NCT02924220, “Genetic Susceptibility and Biomarkers in Listeriosis,” and recruiting NCT03357536, but no validated clinical host-genetic test emerged from the retrieved evidence.

Epigenetic modulation of host susceptibility has been proposed, but no reproducible clinical methylation signature currently diagnoses or predicts listeriosis. Pregnancy-associated immune regulation is clinically important, but should not be represented as a disease-specific inherited epimutation.

Protective factors

There is no established protective human allele or licensed human vaccine. Protective exposures/behaviors are pasteurization, adequate cooking and reheating, avoiding high-risk refrigerated ready-to-eat foods, washing produce, preventing raw-to-ready-food cross-contamination, maintaining clean processing surfaces, and prompt antimicrobial treatment after invasive disease is suspected. (kraus2024listeriainpregnancy—the pages 1-2, kraus2024listeriainpregnancy—the pages 6-7)

3. Phenotypes

Non-invasive illness generally begins within about 24 hours to several days of exposure and is self-limited, with fever, diarrhea, nausea, vomiting, myalgia, and influenza-like symptoms. Invasive disease may appear after roughly 3–70 days, with pregnancy-associated incubation often prolonged. (kraus2024listeriainpregnancy—the pages 4-6)

Suggested phenotype annotations

  • Febrile gastroenteritis: fever HP:0001945, diarrhea HP:0002014, nausea HP:0002018, vomiting HP:0002013, abdominal pain HP:0002027. Usually acute, mild–moderate, self-limited in immunocompetent hosts.
  • Bacteremia/sepsis: bacteremia and sepsis HP:0100806; acute and potentially severe, particularly with comorbidity.
  • CNS disease: meningitis HP:0001287, encephalitis HP:0002383, headache HP:0002315, altered consciousness HP:0004372, seizure HP:0001250, ataxia HP:0001251, cranial-nerve dysfunction where present. Disease may rapidly progress to cerebral edema, hydrocephalus, herniation, rhombencephalitis, or abscess.
  • Maternal–fetal disease: maternal fever and nonspecific myalgia may coexist with miscarriage HP:0005268, stillbirth HP:0003826, premature birth HP:0001622, fetal distress, neonatal respiratory distress, sepsis, or meningitis.
  • Laboratory abnormalities/prognostic correlates: hyponatremia HP:0002902, hyperbilirubinemia HP:0002904, and hyperuricemia HP:0002149.

In a 2024 cohort of 71 confirmed cases, non-neonatal patients had fever in 88%, headache 32%, altered consciousness 25%, vomiting 17%, abdominal pain 12%, and convulsions 8%. Among 12 neonates, fetal distress occurred in 75% and prematurity in 50%. These are hospital-enriched frequencies and should not be generalized to all infected persons. (xu2024clinicalcharacteristicsand pages 1-2)

Quality-of-life studies using EQ-5D, SF-36, or PROMIS were not identified. Nevertheless, ICU admission, cognitive or focal neurologic deficit, seizures, hearing/cranial-nerve dysfunction, and abscess can impair independence and long-term neurodevelopment. In a recent adult cohort, 23.9% of discharged survivors had residual neurologic deficits and 13.0% had brain abscess, demonstrating substantial functional burden.

4. Genetic and molecular information

Distinguishing host from pathogen genetics

There are no human causal genes for listeriosis in the Mendelian-disease sense. Routine WES, WGS, gene panels, CMA, karyotyping, FISH, mitochondrial testing, and repeat-expansion testing are not diagnostic for the infection.

The relevant genetic determinants are predominantly bacterial:

  • prfA: master transcriptional activator of virulence genes.
  • gshF: synthesizes bacterial glutathione that stabilizes active PrfA.
  • inlA/inlB: encode internalins mediating receptor-dependent host-cell entry.
  • hly: encodes listeriolysin O, enabling phagosomal escape.
  • plcA/plcB: phospholipases supporting vacuolar disruption and spread.
  • actA: recruits host actin machinery for cytosolic motility and cell-to-cell dissemination.
  • inlC: interferes with NF-κB-related responses and junctional architecture.
  • inlP: contributes to placental tropism in experimental systems.
  • LIPI-3/lls: listeriolysin-S locus, enriched in lineage I.
  • LIPI-4: CC4-associated hypervirulence locus; mechanism remains unresolved.

Below 30°C an RNA thermoswitch suppresses prfA translation; within a warm host, glutathione activates PrfA. Naturally occurring loss-of-function changes in prfA or gshF occur in approximately 0.1% of isolates and may abolish virulence. (koopmans2023humanlisteriosis pages 5-7)

The 2024 complete genome of attenuated veterinary vaccine strain AUF identified polymorphisms/pseudogenes affecting motility, stress survival, biofilm and virulence-regulatory functions. Because its wild parental strain was unavailable, UV-induced attenuation remains a plausible but not definitive explanation. (feodorova2024completegenomeof pages 11-12)

5. Environmental information

L. monocytogenes behaves as an environmental saprophyte and intracellular pathogen. Relevant reservoirs include soil, water, silage, feces, livestock, wildlife, drains, refrigeration units, and food-processing equipment. Biofilms increase resistance to desiccation and sanitation and permit recurring contamination. In one summarized isolate set, 3.5% were strong and 38.5% moderate biofilm producers. (koncurat2024listeriosischaracteristicsoccurrence pages 1-2)

Diet is the dominant modifiable lifestyle factor. Smoking, exercise, and alcohol are not established direct causes, although alcohol-related liver disease may increase host susceptibility. Conventional “toxins,” ionizing radiation, or pollution are not recognized primary causes. The infectious agent is L. monocytogenes; L. ivanovii is mainly a ruminant pathogen and only rarely causes human infection. (koopmans2023humanlisteriosis pages 1-3)

6. Mechanism and pathophysiology

Ordered causal chain

  1. Ingestion of contaminated food leads to survival of L. monocytogenes through gastric, bile, cold, osmotic, and acid stresses.
  2. Intestinal contact leads to InlA–E-cadherin and InlB–MET-dependent adhesion/internalization, together with alternative uptake by phagocytes and LAP–HSP60-associated junctional remodeling demonstrated chiefly in cell and animal models. (kraus2024listeriainpregnancy—the pages 2-4)
  3. Internalization leads to residence in a primary vacuole/phagosome.
  4. Acidification and PrfA-regulated expression lead to LLO- and PlcA/PlcB-mediated membrane damage, resulting in cytosolic escape before lysosomal killing.
  5. Cytosolic access leads to bacterial replication and innate sensing, while bacterial InlC and related effectors partially suppress NF-κB signaling and neutrophil recruitment. (kraus2024listeriainpregnancy—the pages 4-6)
  6. ActA-mediated actin polymerization leads to actin-comet motility, membrane protrusions, uptake by adjacent cells, and direct cell-to-cell dissemination that reduces extracellular exposure. (kraus2024listeriainpregnancy—the pages 2-4)
  7. Local spread leads to mesenteric/hematogenous dissemination, with early hepatic and splenic capture by macrophages/Kupffer cells and systemic bacteremia when cellular immunity is insufficient.
  8. Bacteremia branches:
  9. Placental/trophoblast invasion leads to placentitis, fetal infection, miscarriage, stillbirth, preterm birth, neonatal sepsis, or meningitis. Internalins and hypervirulent CC4/LIPI-4 are associated with this branch, but parts of the barrier-crossing mechanism remain model-derived or unresolved. (kraus2024listeriainpregnancy—the pages 6-7, koopmans2023humanlisteriosis pages 5-7)
  10. Blood–brain-barrier/choroid-plexus invasion leads to meningitis, meningoencephalitis, rhombencephalitis, edema, hydrocephalus, herniation, or brain abscess.
  11. Other tissue seeding leads to rare endocardial, osteoarticular, ocular, cutaneous, or intra-abdominal disease.
  12. IL-12/IFN-γ-driven macrophage activation, NK responses, and antigen-specific CD8/CD4 T-cell immunity lead to clearance in most immunocompetent hosts; age, pregnancy-associated Th1 attenuation, immunosuppression, and comorbidity lead to failed containment and severe disease.
  13. Bacterial replication plus host inflammatory injury leads to sepsis, neuronal/tissue injury, fetal compromise, organ dysfunction, and death.

Pathways, cells, compartments, and ontology suggestions

  • GO biological process: pathogenesis GO:0009405; entry into host cell GO:0030260; escape from host phagosome GO:0046710; actin-filament polymerization GO:0030041; response to bacterium GO:0009617; inflammatory response GO:0006954; IFN-γ-mediated signaling GO:0060333; phagocytosis GO:0006909.
  • Cell Ontology: intestinal epithelial cell CL:0002563; macrophage CL:0000235; Kupffer cell CL:0000091; neutrophil CL:0000775; dendritic cell CL:0000451; NK cell CL:0000623; T cell CL:0000084; trophoblast CL:0000351; neuron CL:0000540; endothelial cell CL:0000115.
  • GO cellular component: phagocytic vesicle GO:0045335; cytosol GO:0005829; plasma membrane GO:0005886; actin cytoskeleton GO:0015629.
  • Metabolic regulation: bacterial glutathione (CHEBI:16856) activates PrfA; bile resistance enables intestinal survival. A 2024 in-vivo Tn-seq study identified 135 bacterial fitness genes. folD deletion reduced liver growth by 2.5 log10 and impaired cell-to-cell spread; alsR deletion attenuated liver and spleen burdens by 4 and 3 log10, respectively, demonstrating organ-specific folate and D-allose metabolic requirements.

No validated clinical transcriptomic, proteomic, metabolomic, lipidomic, single-cell, or spatial-transcriptomic biomarker is currently used. WGS/wgMLST is the mature omics implementation for isolate typing, virulence profiling, and outbreak detection. (koopmans2023humanlisteriosis pages 5-7, sousa2024currentmethodologiesavailable pages 18-18)

7. Anatomical structures affected

  • Primary portal: gastrointestinal lumen and intestinal epithelium—UBERON:0000160.
  • Reticuloendothelial dissemination: liver UBERON:0002107, spleen UBERON:0002106, blood UBERON:0000178.
  • Nervous system: meninges UBERON:0000363, brain UBERON:0000955, brainstem, and CSF UBERON:0001359.
  • Pregnancy: placenta UBERON:0001987, decidua, trophoblast, amniotic fluid, fetus.
  • Secondary/rare: heart valves, bone/joints, skin, eye, peritoneum, and implanted devices.

At the tissue level, epithelial, endothelial, placental, mononuclear-phagocyte, and nervous tissues are involved. At the subcellular level, the plasma membrane, endocytic/phagocytic vacuole, cytosol, and actin cytoskeleton are central. Lateralization is not characteristic, although focal brainstem or abscess lesions may be asymmetric.

8. Temporal development

Non-invasive gastroenteritis is acute, usually beginning within hours to several days and resolving spontaneously. Invasive disease is acute or subacute after an incubation reported up to approximately 70 days. Pregnancy-associated infection may be mild in the mother yet evolve rapidly toward fetal compromise. (kraus2024listeriainpregnancy—the pages 4-6)

A practical staging concept is: exposure/intestinal colonization → febrile gastroenteritis or asymptomatic phase → bacteremia → CNS, placental, or other focal invasion → complications/recovery/death. This is a mechanistic clinical framework, not an official staging system.

Critical intervention windows include immediate blood cultures and empiric active therapy when a high-risk patient has compatible sepsis/CNS disease, and urgent obstetric evaluation for unexplained fever in pregnancy. Neurolisteriosis and neonatal disease can progress over hours to days; abscess disease requires prolonged therapy and serial imaging. Relapse is uncommon after adequate treatment but may occur with an uncontrolled focus or profound immunosuppression.

9. Inheritance and population epidemiology

Listeriosis is acquired and not inherited. Mendelian inheritance, penetrance, expressivity, anticipation, germline mosaicism, founder mutation, consanguinity, and carrier-frequency fields are not applicable.

Reported incidence varies by surveillance system and population. Recent reviews cite approximately 0.1–1.5 cases/100,000/year globally, while another synthesis gives 0.1–11.3 per million/year. For 2010, the estimated worldwide burden was 23,150 cases, 5,463 deaths, and 172,823 DALYs. Neonatal incidence was summarized as about 3–6/100,000 live births in the United States and 2–8/100,000 in Europe. (kraus2024listeriainpregnancy—the pages 4-6, koopmans2023humanlisteriosis pages 1-3, koopmans2023humanlisteriosis pages 5-7)

The disease occurs worldwide wherever refrigerated ready-to-eat food systems and surveillance exist; rates vary geographically with age structure, food practices, outbreaks, and ascertainment. Older adults and immunocompromised persons dominate non-pregnancy invasive cases. A 2024 adult cohort was 57.1% male with a mean/median reported age around 59 years, but this single-center distribution is not a universal sex ratio.

10. Diagnostics

Clinical and microbiological diagnosis

Definitive diagnosis requires isolation of L. monocytogenes from a normally sterile site: blood, CSF, placenta, amniotic fluid, fetal tissue, joint fluid, or abscess. Culture commonly takes about 36 hours. In pregnancy, placental culture was reported as 80% sensitive versus 55% for maternal blood culture, and placental-biopsy sensitivity as 100%; these figures come from summarized studies and require local validation. Laboratories should not dismiss Gram-positive rods as “diphtheroids” when the syndrome fits. (kraus2024listeriainpregnancy—the pages 4-6, kraus2024listeriainpregnancy—the pages 6-7)

For suspected neurolisteriosis, perform blood cultures and lumbar puncture unless contraindicated. CSF generally shows bacterial meningitis—pleocytosis, elevated protein, and reduced glucose—but Gram stain can be insensitive. MRI is preferred for rhombencephalitis, abscess, cranial-nerve, or persistent focal findings; CT is useful urgently for mass effect/hydrocephalus. Placental histology may show microabscesses/inflammation, but culture establishes etiology.

Stool culture is not recommended to diagnose invasive listeriosis or screen asymptomatic exposed people because carriage can be transient and a negative result does not exclude systemic disease. Serology lacks adequate clinical utility. Isolate WGS/wgMLST supports outbreak linkage and surveillance, not rapid bedside exclusion. (koopmans2023humanlisteriosis pages 5-7)

Differential diagnosis

  • Gastroenteritis: Salmonella, Campylobacter, Shiga-toxin-producing E. coli, norovirus, and other foodborne illness.
  • Sepsis/meningitis: Streptococcus pneumoniae, Neisseria meningitidis, group-B streptococcus, enteric Gram-negative bacilli, HSV encephalitis, tuberculosis, fungal meningitis, and brain abscess pathogens.
  • Rhombencephalitis: HSV, enterovirus, tuberculosis, autoimmune/demyelinating brainstem disease, stroke, or neoplasm.
  • Pregnancy fever/fetal compromise: pyelonephritis, influenza/COVID-19, chorioamnionitis from other bacteria, toxoplasmosis, syphilis, CMV, and placental abruption.

A critical therapeutic clue is that routine third-generation cephalosporin meningitis regimens do not reliably cover Listeria; an aminopenicillin is required when age or immune status creates risk.

Genetic/omics testing and screening

Human WES/WGS, gene panels, CMA, karyotype, FISH, mtDNA, and repeat testing have no routine role. Bacterial WGS is valuable for public-health surveillance and resistance/virulence characterization. There is no newborn, carrier, cascade, prenatal-genetic, or general-population screening program for listeriosis.

11. Outcome and prognosis

Listeriosis has no meaningful 5- or 10-year “survival rate”; acute case fatality and neurologic/obstetric outcomes are the appropriate measures.

In the 2024 Xi’an cohort, fatality was 42% in neonates versus 17% in non-neonates and 36% in neurolisteriosis versus 12% in bacteremia. CNS involvement, hyperbilirubinemia, and hyponatremia predicted fatality; hyperuricemia added risk among non-neonates. Of 23 maternal cases, only two had uneventful obstetric outcomes despite no maternal deaths. (xu2024clinicalcharacteristicsand pages 1-2)

A separate 63-adult retrospective cohort reported 27.0% in-hospital mortality, 44.4% ICU admission, residual neurologic deficits in 23.9% of discharged survivors, and brain abscess in 13.0%. Thus, surviving uncomplicated gastroenteritis generally recover fully, whereas neonatal and CNS disease can cause death, developmental impairment, seizures, cognitive deficits, or other lasting disability.

Early gestational infection has especially poor fetal prognosis. Reviews report miscarriage in approximately 65% of first-trimester infections versus 26% diagnosed later; each additional gestational week at infection was associated with improved fetal survival in one summarized analysis. These estimates are vulnerable to referral and publication bias. (kraus2024listeriainpregnancy—the pages 6-7, koncurat2024listeriosischaracteristicsoccurrence pages 8-9)

12. Treatment

Pharmacotherapy and strategy

Treatment evidence is based largely on microbiology, observational series, animal data, and expert consensus; randomized comparative trials are lacking.

  • Adult neurolisteriosis: intravenous ampicillin or amoxicillin totaling about 12 g/day for at least 21 days. Consider short-course gentamicin in severe disease, balancing uncertain incremental benefit against nephrotoxicity/ototoxicity.
  • Brain abscess or rhombencephalitis: active β-lactam for at least six weeks, individualized with serial MRI/CT.
  • Bacteremia without deep focus: aminopenicillin-based therapy, commonly about two weeks after clinical response and culture clearance, longer when immunosuppression or focal infection persists.
  • Pregnancy: IV ampicillin/amoxicillin 6–12 g/day; one French approach uses amoxicillin 100 mg/kg/day for two weeks or until delivery, with gentamicin 5 mg/kg/day for 3–5 days in selected severe cases.
  • Neonatal early-onset disease: parenteral ampicillin/amoxicillin 100–300 mg/kg/day for 14 days; days 8–28 or meningitis generally require 21 days. Gentamicin, e.g. 2 mg/kg for seven days in the cited synthesis, may be added according to neonatal guidance and renal monitoring.
  • β-lactam allergy/intolerance: trimethoprim–sulfamethoxazole is the best-established alternative. Meropenem, linezolid, rifampicin-containing combinations, moxifloxacin, fosfomycin, or chloramphenicol may be considered with specialist input, but superiority is unproven. (koopmans2023humanlisteriosis pages 26-27)

CHEBI suggestions: ampicillin CHEBI:28971; amoxicillin CHEBI:2676; gentamicin CHEBI:27412; trimethoprim CHEBI:45924; sulfamethoxazole CHEBI:9332. NCIT suggestions: Antibiotic Therapy C15614; Intravenous Route of Administration C38276; Intensive Care C53511; Physical Therapy C15360 and rehabilitation terms for neurologic sequelae.

Supportive care includes sepsis management, airway/ventilation, seizure control, intracranial-pressure management, obstetric/fetal monitoring, neonatal intensive care, nutrition, and neurologic/physical/occupational/speech rehabilitation. Drainage or surgery is reserved for selected abscesses, infected prostheses, endocarditis, or other source-control needs.

Recent isolates remain broadly susceptible to aminopenicillins. The 2024 Xi’an cohort found only two ampicillin-resistant and one penicillin-resistant isolate; a 63-case Hungarian cohort reported 100% in-vitro susceptibility to ampicillin and meropenem, 97.7% to trimethoprim–sulfamethoxazole, and 86.0% to gentamicin. Multidrug-resistant strains nevertheless occur, supporting isolate-level susceptibility testing. (xu2024clinicalcharacteristicsand pages 1-2, koopmans2023humanlisteriosis pages 26-27, koncurat2024listeriosischaracteristicsoccurrence pages 8-9)

No approved gene, cell, RNA, checkpoint, or precision-genotype therapy treats listeriosis. Attenuated Listeria vectors under study for cancer immunotherapy are conceptually distinct and should not be represented as listeriosis treatment.

13. Prevention

Primary prevention

No licensed human vaccine exists. High-risk persons should avoid unpasteurized milk/dairy, refrigerated pâté or meat spreads, unheated deli meats/hot dogs, refrigerated smoked seafood unless cooked, and high-risk soft cheeses unless made from pasteurized milk under controlled production. Reheat ready-to-eat meats until steaming, wash produce, separate raw from cooked foods, clean refrigerators and preparation surfaces, and observe storage limits. (kraus2024listeriainpregnancy—the pages 6-7)

Food-industry measures include hazard analysis, environmental sampling, sanitation of drains/equipment, temperature and shelf-life control, pasteurization/cooking, product recall, and WGS-based surveillance linking clinical, food, and environmental isolates. High-pressure processing at approximately 100–600 MPa can reduce L. monocytogenes below detection in some foods, although sublethally injured cells may recover, so it complements rather than replaces validated controls.

Secondary and tertiary prevention

There is no routine asymptomatic stool, blood, prenatal, or population screening. Risk stratification is clinical: pregnancy, advanced age, immunosuppression, and major comorbidity should lower the threshold for evaluation after compatible illness or outbreak exposure. Secondary prevention is prompt culture and active aminopenicillin therapy. Tertiary prevention comprises source control, adequate treatment duration, repeat cultures where indicated, CNS imaging, fetal/neonatal monitoring, and rehabilitation.

Routine antibiotic prophylaxis for an asymptomatic person who ate a recalled product is generally unsupported; clinical evaluation is appropriate if fever or invasive symptoms arise, particularly during pregnancy or immunosuppression.

14. Other species and natural disease

Natural listeriosis occurs across mammals, birds, wildlife, aquatic animals, and invertebrates; one review noted isolation across 42 mammalian and 29 avian species. Cattle (NCBI Taxon 9913), sheep (9940), and goats (9925) are particularly important. Ruminant disease includes encephalitis/meningoencephalitis (“circling”), septicemia, abortion, stillbirth, and neonatal loss. Abortions usually occur in the last gestational third and may affect up to 20% of a herd/flock during outbreaks. Ruminants can shed organisms and contaminate silage, milk, meat, soil, and processing environments, creating a One Health bridge to human exposure. (koncurat2024listeriosischaracteristicsoccurrence pages 1-2, koncurat2024listeriosischaracteristicsoccurrence pages 8-9)

L. ivanovii is primarily pathogenic in ruminants; L. innocua is usually nonpathogenic but virulent isolates exist. A 2024 study recovered L. monocytogenes, L. innocua, and L. ivanovii from stranded Mediterranean sea turtles, with little difference in virulence-gene distribution between some turtle and human strains, illustrating wildlife/environmental circulation rather than proving frequent turtle-to-human transmission. (renzo2024genomiccharacterizationof pages 14-15)

Breed-specific VBO associations and orthologous host “disease genes” are not applicable because natural disease is infectious rather than a breed-linked monogenic trait. An attenuated AUF L. monocytogenes live veterinary vaccine has been used in some settings since the 1960s; its 2,942,932-bp genome contains more than 2,800 coding sequences, 17 pseudogenes, five annotated resistance genes, and 56/92 surveyed virulence genes. This does not constitute a licensed human vaccine. (feodorova2024completegenomeof pages 11-12)

15. Model organisms and advanced experimental systems

  • Conventional mouse: foundational for systemic infection, innate/adaptive immunity, hepatic/splenic colonization, bacterial mutants, and vaccine-vector work. Limitation: murine E-cadherin is poorly recognized by InlA, so ordinary mice incompletely model human oral invasion and placental tropism.
  • Humanized E-cadherin knock-in mouse: improves InlA-dependent intestinal entry but does not eliminate all interspecies placental and immune differences.
  • Gerbil/guinea pig: receptors and reproductive anatomy can better reproduce selected intestinal or maternal–fetal steps; fewer genetic tools are available.
  • Zebrafish larvae: permit live imaging of phagocyte–pathogen interactions; temperature and anatomy limit direct clinical translation.
  • Invertebrates, including Galleria mellonella: inexpensive virulence screening but lack mammalian adaptive immunity and relevant barriers.
  • Cell culture: Caco-2 epithelial cells, macrophage lines such as RAW264.7, fibroblasts, endothelial cells, and trophoblasts dissect adhesion, invasion, escape, actin motility, and cytotoxicity.
  • Ex-vivo and organotypic systems: placental explants, intestinal organoids, blood–brain-barrier cultures, and brain slices offer human tissue relevance but lack full circulation and systemic immunity.

A 2024 RECON/Akr1c13-disrupted mouse enabled high-dose in-vivo Tn-seq and identified 135 pathogen fitness genes, including organ-specific folD and alsR phenotypes. This exemplifies current functional genomics: it discovers bacterial dependencies but does not itself establish human treatment targets.

Recent developments and expert interpretation, 2023–2024

  1. The 2023 Clinical Microbiology Reviews synthesis consolidated modern clinical, genomic, and mechanistic understanding and emphasized that cross-border WGS data sharing improves outbreak-source identification. (koopmans2023humanlisteriosis pages 1-3, koopmans2023humanlisteriosis pages 5-7)
  2. Two 2024 hospital cohorts quantified persistently high mortality and neurologic sequelae despite aminopenicillin susceptibility, indicating that delayed recognition, CNS invasion, age, and host illness—not antimicrobial resistance alone—drive outcomes. (xu2024clinicalcharacteristicsand pages 1-2)
  3. Current pathogen-genomics work is moving from lineage description toward WGS/machine-learning virulence prediction, but genotype alone cannot yet replace phenotypic or epidemiologic assessment. Some nominally nonpathogenic isolates invade cultured cells despite lacking major LIPI loci. (sousa2024currentmethodologiesavailable pages 18-18)
  4. In-vivo Tn-seq has exposed organ-specific metabolic requirements, while complete sequencing of long-used attenuated veterinary strains offers rational starting points for vaccine-vector safety assessment. (feodorova2024completegenomeof pages 11-12)
  5. The expert consensus remains that prevention and early empiric aminopenicillin coverage in the correct risk groups have greater immediate clinical value than experimental host-genetic or omics biomarkers.

Selected exact source quotations

  • Koopmans et al., published March 2023: “Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal sepsis.” DOI: https://doi.org/10.1128/cmr.00060-19. (koopmans2023humanlisteriosis pages 1-3)
  • Xu et al., published May 2024: “Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.” DOI: https://doi.org/10.1007/s40121-024-00986-3. (xu2024clinicalcharacteristicsand pages 1-2)
  • Feodorova et al., published June 2024, described AUF as an attenuated strain “successfully used since the 1960s as a live whole-cell veterinary vaccine.” DOI: https://doi.org/10.1038/s41597-024-03440-8. (feodorova2024completegenomeof pages 11-12)

Knowledge-base caveats

Frequencies from tertiary-hospital cohorts overrepresent severe disease. Associations between clonal complexes and clinical syndromes are pathogen-level epidemiologic associations, not deterministic patient biomarkers. Most detailed barrier-crossing and intracellular mechanisms derive from in-vitro, organoid, or animal experiments; they are biologically compelling but should be labeled model-derived where direct human demonstration is unavailable. Human causal-variant, chromosomal, pharmacogenomic, validated omics-biomarker, licensed-vaccine, and population-screening fields should presently be recorded as not established/not applicable, rather than filled by analogy.

References

  1. (koopmans2023humanlisteriosis pages 1-3): Merel M. Koopmans, Matthijs C. Brouwer, José A. Vázquez-Boland, and Diederik van de Beek. Human listeriosis. Clinical Microbiology Reviews, Mar 2023. URL: https://doi.org/10.1128/cmr.00060-19, doi:10.1128/cmr.00060-19. This article has 374 citations and is from a highest quality peer-reviewed journal.

  2. (xu2024clinicalcharacteristicsand pages 1-2): Wen Xu, Mei-Juan Peng, Lin-Shan Lu, Zhen-Jun Guo, A-Min Li, Jing Li, Yan Cheng, Jia-Yu Li, Yi-Jun Li, Jian-Qi Lian, Yu Li, Yang Sun, Wei-Lu Zhang, and Ye Zhang. Clinical characteristics and fatality risk factors for patients with listeria monocytogenes infection: a 12-year hospital-based study in xi’an, china. Infectious Diseases and Therapy, 13:1359-1378, May 2024. URL: https://doi.org/10.1007/s40121-024-00986-3, doi:10.1007/s40121-024-00986-3. This article has 10 citations and is from a peer-reviewed journal.

  3. (kraus2024listeriainpregnancy—the pages 6-7): Vladimír Kraus, Beáta Čižmárová, and Anna Birková. Listeria in pregnancy—the forgotten culprit. Microorganisms, 12(10):2102, Oct 2024. URL: https://doi.org/10.3390/microorganisms12102102, doi:10.3390/microorganisms12102102. This article has 29 citations.

  4. (kraus2024listeriainpregnancy—the pages 2-4): Vladimír Kraus, Beáta Čižmárová, and Anna Birková. Listeria in pregnancy—the forgotten culprit. Microorganisms, 12(10):2102, Oct 2024. URL: https://doi.org/10.3390/microorganisms12102102, doi:10.3390/microorganisms12102102. This article has 29 citations.

  5. (koopmans2023humanlisteriosis pages 5-7): Merel M. Koopmans, Matthijs C. Brouwer, José A. Vázquez-Boland, and Diederik van de Beek. Human listeriosis. Clinical Microbiology Reviews, Mar 2023. URL: https://doi.org/10.1128/cmr.00060-19, doi:10.1128/cmr.00060-19. This article has 374 citations and is from a highest quality peer-reviewed journal.

  6. (kraus2024listeriainpregnancy—the pages 1-2): Vladimír Kraus, Beáta Čižmárová, and Anna Birková. Listeria in pregnancy—the forgotten culprit. Microorganisms, 12(10):2102, Oct 2024. URL: https://doi.org/10.3390/microorganisms12102102, doi:10.3390/microorganisms12102102. This article has 29 citations.

  7. (kraus2024listeriainpregnancy—the pages 4-6): Vladimír Kraus, Beáta Čižmárová, and Anna Birková. Listeria in pregnancy—the forgotten culprit. Microorganisms, 12(10):2102, Oct 2024. URL: https://doi.org/10.3390/microorganisms12102102, doi:10.3390/microorganisms12102102. This article has 29 citations.

  8. (koopmans2023humanlisteriosis pages 26-27): Merel M. Koopmans, Matthijs C. Brouwer, José A. Vázquez-Boland, and Diederik van de Beek. Human listeriosis. Clinical Microbiology Reviews, Mar 2023. URL: https://doi.org/10.1128/cmr.00060-19, doi:10.1128/cmr.00060-19. This article has 374 citations and is from a highest quality peer-reviewed journal.

  9. (koncurat2024listeriosischaracteristicsoccurrence pages 1-2): Ana Končurat and Tomislav Sukalić. Listeriosis: characteristics, occurrence in domestic animals, public health significance, surveillance and control. Oct 2024. URL: https://doi.org/10.3390/microorganisms12102055, doi:10.3390/microorganisms12102055. This article has 30 citations.

  10. (koncurat2024listeriosischaracteristicsoccurrence pages 8-9): Ana Končurat and Tomislav Sukalić. Listeriosis: characteristics, occurrence in domestic animals, public health significance, surveillance and control. Oct 2024. URL: https://doi.org/10.3390/microorganisms12102055, doi:10.3390/microorganisms12102055. This article has 30 citations.

  11. (feodorova2024completegenomeof pages 11-12): Valentina A. Feodorova, Sergey S. Zaitsev, Mariya A. Khizhnyakova, Maxim S. Lavrukhin, Yury V. Saltykov, Alexey D. Zaberezhny, and Olga S. Larionova. Complete genome of the listeria monocytogenes strain auf, used as a live listeriosis veterinary vaccine. Scientific Data, Jun 2024. URL: https://doi.org/10.1038/s41597-024-03440-8, doi:10.1038/s41597-024-03440-8. This article has 6 citations and is from a peer-reviewed journal.

  12. (sousa2024currentmethodologiesavailable pages 18-18): Mariana Sousa, Rui Magalhães, Vânia Ferreira, and Paula Teixeira. Current methodologies available to evaluate the virulence potential among listeria monocytogenes clonal complexes. Frontiers in Microbiology, Oct 2024. URL: https://doi.org/10.3389/fmicb.2024.1425437, doi:10.3389/fmicb.2024.1425437. This article has 8 citations and is from a peer-reviewed journal.

  13. (renzo2024genomiccharacterizationof pages 14-15): Ludovica Di Renzo, Maria Elisabetta De Angelis, Marina Torresi, Giulia Mariani, Federica Pizzurro, Luana Fiorella Mincarelli, Emanuele Esposito, Maria Oliviero, Doriana Iaccarino, Fabio Di Nocera, Gianluigi Paduano, Giuseppe Lucifora, Cesare Cammà, Nicola Ferri, and Francesco Pomilio. Genomic characterization of listeria monocytogenes and other listeria species isolated from sea turtles. Apr 2024. URL: https://doi.org/10.3390/microorganisms12040817, doi:10.3390/microorganisms12040817. This article has 4 citations.

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