Yersinia Enterocolitica Infectious Disease

Infectious Disease MONDO:0042370 Pathograph 21 Show in embeddings browser Yersinia infectious disease Bacterial enteritis

Yersinia enterocolitica infectious disease is a foodborne zoonotic infection in which ingestion of Yersinia enterocolitica from contaminated pork or other vehicles leads to invasive ileal enterocolitis, mesenteric lymphadenitis, and pseudoappendicitis, with septicemia and focal hepatic or splenic abscesses in vulnerable iron-overloaded or immunocompromised hosts.

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1
Definitions
8
Pathophys.
11
Phenotypes
21
Pathograph
1
Genes
1
Medical Actions
3
Models
1
Deep Research
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Classifications

Harrison's Part
INFECTIOUS DISEASES
📘

Definitions

1
Intestinal yersiniosis clinical spectrum
Intestinal yersiniosis spans enteritis, terminal ileitis with mesenteric lymphadenitis or pseudoappendicitis, and septicemic disease with splenic or hepatic abscesses.
CASE_DEFINITION
Show evidence (1 reference)
PMID:15254824 SUPPORT REVIEW SYNTHESIS Other
"Intestinal yersiniosis may manifest in humans as (1) enteritis, (2) terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3) septicemia leading to focal abscesses in spleen and liver."
The review defines the major enteric, pseudoappendiceal, and septicemic clinical forms captured by this disease entry.
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Pathophysiology

8
Pork-Borne Yersinia enterocolitica Ingestion
Infection starts when viable pathogenic Y. enterocolitica reaches the small intestine after ingestion of contaminated raw or undercooked pork or another fecally contaminated vehicle.
Downstream
Invasin-Mediated Peyer's Patch Entry Enteric delivery positions bacteria at the follicle-associated epithelium over Peyer's patches for M-cell translocation.
YstA Heat-Stable Enterotoxin Secretion Pathogenic organisms entering the intestinal lumen can express the chromosomally encoded YstA enterotoxin branch that contributes to acute diarrheal enteritis.
Show evidence (1 reference)
PMID:26403101 SUPPORT REVIEW SYNTHESIS Other
"Swine play an important role as a reservoir of Y. enterocolitica and insufficiently thermally processed pork is the main source of infection to humans."
The review supports contaminated pork ingestion as a major initiating exposure for human yersiniosis.
Invasin-Mediated Peyer's Patch Entry
Yersinia invasin binds host beta-1 integrins on intestinal epithelial and M cells, enabling internalization across the ileal mucosa and entry into Peyer's patch lymphoid tissue.
M cell of gut CL:0000682 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves M cell of gut (CL:0000682). CL:0000682 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 symbiont entry into host cell (GO:0046718). GO:0046718 is a biological process from the Gene Ontology.
small intestine Peyer's patch UBERON:0003454 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in small intestine Peyer's patch (UBERON:0003454). UBERON:0003454 is an anatomical location from the Uberon multi-species anatomy ontology.
Animal models
Oral Yersinia enterocolitica mouse infection Mus musculus partially recapitulates The model uses oral infection to capture the intestinal entry context in which Peyer's patch invasion and mucosal innate lymphoid responses are measured.
Downstream
Phagocyte-Associated Mesenteric Dissemination Organisms entering across Peyer's patches and lamina propria are carried by mononuclear phagocytes toward mesenteric lymph nodes and, in severe infection, deeper reticuloendothelial sites.
Show evidence (1 reference)
PMID:26731748 SUPPORT In Vitro
"These bacteria can cross the intestinal mucosa, and invade eukaryotic cells by binding to host β1 integrins, a process mediated by the bacterial effector protein invasin."
Intestinal epithelial-cell assays support beta-1 integrin binding by invasin as a host-entry mechanism.
Phagocyte-Associated Mesenteric Dissemination
After mucosal entry, Y. enterocolitica can associate with CD103-positive dendritic cells and monocyte-derived cells in the lamina propria and spread to mesenteric lymph nodes, spleen, and liver.
dendritic cell CL:0000451 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves dendritic cell (CL:0000451). CL:0000451 is a cell type from the Cell Ontology. 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.
mesenteric lymph node UBERON:0002509 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in mesenteric lymph node (UBERON:0002509). UBERON:0002509 is an anatomical location from the Uberon multi-species anatomy ontology.
Animal models
Rodent yersiniosis model Rodents recapitulates Mouse and rabbit infection reproduce Peyer's-patch entry and downstream spread into lymph nodes, spleen, and liver, while rat infection can model the post-infectious arthritis branch.
Downstream
pYV Type III Secretion and Yop Effector Injection Disseminating pathogenic organisms use the pYV-encoded type III secretion apparatus to deliver anti-host Yop proteins into interacting phagocytes.
Deferoxamine-Potentiated Systemic Yersinia Replication Organisms that reach reticuloendothelial sites can cause septicemia and focal abscesses when iron overload or deferoxamine exposure permits systemic replication.
Show evidence (1 reference)
PMID:27107739 SUPPORT Model Organism
"After colonisation of the small intestine Ye invades the Peyer's patches (PPs) via M cells and disseminates to the mesenteric lymph nodes (MLNs), spleen and liver."
Oral infection in mice supports spread from the small intestine to regional lymph nodes and systemic reticuloendothelial organs.
Cold-Stored Blood Product Yersinia Inoculation
Cold-stored red blood cell products can permit contaminating Y. enterocolitica to proliferate before transfusion-associated bloodstream inoculation.
Downstream
Bacteremia Transfusion of a contaminated blood product can seed bacteria directly into the bloodstream and produce severe septic disease.
Show evidence (1 reference)
PMID:33341965 SUPPORT In Vitro
"two Y. enterocolitica strains reached the stationary phase between days 14 and 21 of RBCC storage with a bacterial concentration of approximately 109 CFU/ml."
The ex-vivo blood-product study shows that Y. enterocolitica can proliferate during refrigerated red-blood-cell storage.
pYV Type III Secretion and Yop Effector Injection
Pathogenic Y. enterocolitica carries the pYV plasmid, whose Ysc secretion machinery exports Yop proteins into host immune cells.
protein secretion by the type III secretion system GO:0030254 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves protein secretion by the type III secretion system (GO:0030254). GO:0030254 is a biological process from the Gene Ontology.
Downstream
YopJ-Driven Macrophage Survival-Pathway Blockade Translocated YopJ/YopP blocks macrophage survival signaling and promotes death of innate immune cells.
Show evidence (1 reference)
PMID:8709853 SUPPORT In Vitro
"The components of the secretion machinery are encoded by three loci on the pYV plasmid: virA, virB, and virC."
The mutational analysis maps the Yop type III secretion apparatus to the pYV virulence plasmid.
YopJ-Driven Macrophage Survival-Pathway Blockade
YopJ and related Yop effectors suppress macrophage survival and innate immune signaling, impairing bacterial clearance and amplifying ileal and mesenteric inflammation.
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.
effector-mediated suppression of host innate immune response GO:0140403 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves effector-mediated suppression of host innate immune response (GO:0140403). GO:0140403 is a biological process from the Gene Ontology. apoptotic process GO:0006915 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves apoptotic process (GO:0006915). GO:0006915 is a biological process from the Gene Ontology.
Animal models
Ye WAP-314-infected C57BL/6 mouse Mus musculus partially recapitulates The model measures a downstream anti-inflammatory myeloid response to infection in the same mesenteric and splenic compartments seeded by invasive Y. enterocolitica.
Downstream
Ileitis Anti-phagocyte Yop effector activity lets organisms persist in the ileal lymphoid tissue where terminal ileitis develops.
Lymphadenitis Failed phagocyte clearance and Yop effector delivery support bacterial persistence in mesenteric lymph nodes.
Show evidence (1 reference)
PMID:22563435 SUPPORT In Vitro
"Yersinia outer protein J (YopJ) is a type III secretion system (T3SS) effector of pathogenic Yersinia (Yersinia pestis, Yersinia enterocolitica and Yersinia pseudotuberculosis) that is secreted into host cells."
The paper identifies YopJ as a type III-secreted effector used by pathogenic Yersinia species, including Y. enterocolitica.
Deferoxamine-Potentiated Systemic Yersinia Replication
Deferoxamine provides chelated iron that pathogenic Y. enterocolitica can use under iron limitation, allowing invasive growth and septicemia in iron-overloaded hosts.
Downstream
Bacteremia Ferrioxamine-supported growth can amplify systemic organisms into Y. enterocolitica septicemia.
Splenic abscess Septicemic Y. enterocolitica can seed reticuloendothelial organs and form splenic abscesses.
Liver abscess Septicemic Y. enterocolitica can seed reticuloendothelial organs and form hepatic abscesses.
Show evidence (1 reference)
PMID:12019084 SUPPORT BACKGROUND Human Clinical
"Deferoxamine, a drug used to treat patients with iron overload, has the capacity to promote systemic Y. enterocolitica infections in humans."
The deferoxamine study supports the clinical link between this iron chelator and systemic Y. enterocolitica infection.
YstA Heat-Stable Enterotoxin Secretion
Pathogenic Y. enterocolitica biotypes commonly carry ystA and can produce heat-stable enterotoxin independently of the pYV virulence plasmid, contributing a luminal toxin branch to acute diarrhea.
Downstream
Diarrhea Heat-stable enterotoxin production in the intestinal lumen contributes to diarrheal enteritis during yersiniosis.
Show evidence (2 references)
PMID:28400007 SUPPORT In Vitro
"The most common virulence-associated gene in pathogenic Y. enterocolitica proved to be ystA"
Virulence-gene screening identified ystA as a common marker of pathogenic Y. enterocolitica biotypes.
PMID:30961808 SUPPORT In Vitro
"The results of this study indicate that the presence of pYV does not affect the enterotoxin-producing ability of Y. enterocolitica strains."
The pig-isolate assay supports YstA enterotoxin production as an intestinal branch separable from the pYV type III secretion branch.
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Pathograph

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

11
Cardiovascular 2
Lymphadenitis HP:0002840 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is mesenteric lymphadenitis, annotated with Lymphadenitis (HP:0002840). HP:0002840 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:15254824 SUPPORT REVIEW SYNTHESIS Other
"Intestinal yersiniosis may manifest in humans as (1) enteritis, (2) terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3) septicemia leading to focal abscesses in spleen and liver."
The review explicitly lists mesenteric lymphadenitis as part of the appendicitis-mimicking presentation.
Splenic abscess HP:0025059 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Splenic abscess (HP:0025059). HP:0025059 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:15254824 SUPPORT REVIEW SYNTHESIS Other
"septicemia leading to focal abscesses in spleen and liver"
The review explicitly includes splenic abscesses in septicemic intestinal yersiniosis.
Digestive 3
Diarrhea HP:0002014 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Diarrhea (HP:0002014). HP:0002014 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26403101 SUPPORT REVIEW SYNTHESIS Other
"Yersiniosis usually appears with gastrointestinal disturbances in children, whereas in adults it manifests in a pseudo-appendix form."
The review supports gastrointestinal disturbance as a common clinical manifestation of human yersiniosis.
Ileitis HP:0032564 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ileitis (HP:0032564). HP:0032564 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:15254824 SUPPORT REVIEW SYNTHESIS Other
"Intestinal yersiniosis may manifest in humans as (1) enteritis, (2) terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3) septicemia leading to focal abscesses in spleen and liver."
The review explicitly lists terminal ileitis in the intestinal yersiniosis spectrum.
Liver abscess HP:0100523 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Liver abscess (HP:0100523). HP:0100523 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:15254824 SUPPORT REVIEW SYNTHESIS Other
"septicemia leading to focal abscesses in spleen and liver"
The review explicitly includes hepatic abscesses in septicemic intestinal yersiniosis.
Eye 1
Uveitis HP:0000554 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Uveitis (HP:0000554). HP:0000554 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:8363822 SUPPORT REVIEW SYNTHESIS Other
"Yersinia enterocolitica infection in humans causes a broad spectrum of diseases ranging from acute bowel disease to extraintestinal manifestations such as reactive arthritis, erythema nodosum and uveitis."
The rodent-model review lists uveitis as an extraintestinal manifestation of human Y. enterocolitica infection.
Immune 1
Erythema nodosum HP:0012219 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Erythema nodosum (HP:0012219). HP:0012219 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26403101 SUPPORT REVIEW SYNTHESIS Other
"erythema nodosum, induced by Y. enterocolitica, constitutes over 20% of all erythema cases"
The review identifies erythema nodosum as a Y. enterocolitica-induced extraintestinal manifestation.
Metabolism 2
Fever 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:26403101 SUPPORT REVIEW SYNTHESIS Other
"gastroenterocolitis accompanied by fever and severe, often bloody, diarrhea"
The review lists fever among manifestations accompanying intestinal yersiniosis.
Bacteremia HP:0031864 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bacteremia (HP:0031864). HP:0031864 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:15254824 SUPPORT REVIEW SYNTHESIS Other
"Intestinal yersiniosis may manifest in humans as (1) enteritis, (2) terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3) septicemia leading to focal abscesses in spleen and liver."
Septicemia establishes bloodstream dissemination as a severe manifestation of intestinal yersiniosis.
Constitutional 1
Abdominal pain 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:26403101 SUPPORT REVIEW SYNTHESIS Other
"Vomiting and abdominal pain lasting for 1-3 weeks are also observed"
The review lists abdominal pain among human yersiniosis manifestations.
Other 1
Reactive arthritis MONDO:0017376 Mondo Disease Ontology (MONDO) Relation: this clinical feature is this phenotype This clinical feature is reactive arthritis (MONDO:0017376). MONDO:0017376 is a phenotype from the Mondo Disease Ontology.
Show evidence (1 reference)
PMID:40473988 SUPPORT REVIEW SYNTHESIS Other
"The most common agents include Chlamydia trachomatis, Ureaplasma urealyticum, and Neisseria gonorrhea for the venereal type and Salmonella enteriditis, Shigella flexneri, Yersinia enterocolitica for the post-enteric type."
The review names Y. enterocolitica as a common post-enteric trigger of reactive arthritis.
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Genetic Associations

1
HLA-B27 (HLA-B27 predisposes to Yersinia enterocolitica-associated reactive arthritis)
relationship_type: SUSCEPTIBILITY
Show evidence (1 reference)
PMID:7221767 SUPPORT BACKGROUND Human Clinical
"A reactive or post-infectious arthritis is a well-known complication of yersinia enterocolitica infection and tends to occur in patients with the HLA-B27 haplotype."
The case-report background identifies HLA-B27 as a host haplotype associated with the post-infectious arthritis complication of Y. enterocolitica.
💊

Medical Actions

1
Antibiotic therapy for invasive yersiniosis
Action: antibiotic therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antibiotic therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. Ontology label: Antibiotic Therapy NCIT:C15620
Agent: ceftriaxone CHEBI:29007 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ceftriaxone (CHEBI:29007). CHEBI:29007 is a therapeutic agent from Chemical Entities of Biological Interest. ciprofloxacin CHEBI:100241 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ciprofloxacin (CHEBI:100241). CHEBI:100241 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Third-generation cephalosporins, fluoroquinolones, and susceptibility-guided alternatives are used for severe invasive disease, while ampicillin and cefazolin are unreliable because clinical Y. enterocolitica strains are intrinsically resistant to those agents.
Mechanism Target:
INHIBITS Phagocyte-Associated Mesenteric Dissemination — Active antibiotics reduce viable organisms responsible for systemic dissemination in invasive yersiniosis.
INHIBITS YstA Heat-Stable Enterotoxin Secretion — Active antibiotics reduce the viable enteric bacterial population that can produce YstA enterotoxin during symptomatic intestinal disease.
Show evidence (2 references)
PMID:10803262 SUPPORT In Vitro
"Third-generation cephalosporins such as cefotaxime and ceftriaxone and a fluoroquinolone (ciprofloxacin) were the most active antimicrobial agents, tested followed by aztreonam, imipenem, trimethoprim, tetracycline, gentamicin, chloramphenicol, amoxycillin/clavulanate, cefaclor, cefuroxime,..."
Susceptibility testing of clinical serotype O:3 isolates supports third-generation cephalosporins and ciprofloxacin as active agents against Y. enterocolitica.
PMID:10803262 SUPPORT In Vitro
"Almost all tested strains were resistant to ampicillin and cefazolin"
The same clinical-isolate susceptibility series supports the intrinsic ampicillin and cefazolin resistance caveat in the treatment description.
🌍

Environmental Factors

3
Pork and dairy food exposure
Pork and dairy products are repeatedly implicated food vehicles for non-pestis Yersinia outbreaks, with raw or undercooked pork providing the central route from the swine reservoir to human intestinal exposure.
Show evidence (2 references)
PMID:42720049 SUPPORT Human Clinical
"Pork (46%) and dairy (18%) products were the most frequently identified food vehicles"
Pork and dairy were the leading outbreak vehicles in the United States non-pestis Yersinia outbreak review.
PMID:29307129 SUPPORT Other
"Yersinia enterocolitica was isolated from 35 out of 376 (9.31%) samples."
The slaughterhouse survey quantifies Y. enterocolitica tonsillar carriage in pigs, supporting the food-animal reservoir rather than human disease prevalence.
Mechanism Target:
TRIGGERS Pork-Borne Yersinia enterocolitica Ingestion — Consumption of contaminated pork or dairy delivers viable Y. enterocolitica to the intestine.
Show evidence (2 references)
PMID:26403101 SUPPORT REVIEW SYNTHESIS Other
"Swine play an important role as a reservoir of Y. enterocolitica and insufficiently thermally processed pork is the main source of infection to humans."
The review supports undercooked pork as a major exposure route for human ingestion of Y. enterocolitica.
PMID:42720049 SUPPORT Human Clinical
"Pork (46%) and dairy (18%) products were the most frequently identified food vehicles"
The outbreak review identifies pork and dairy as the most common food vehicles in United States non-pestis Yersinia outbreaks.
Cold-chain persistence and food-processing contamination
Psychrotolerance and biofilm formation let Y. enterocolitica persist across refrigerated food-processing and retail settings, increasing the chance that contaminated food remains infectious at consumption.
Show evidence (1 reference)
PMID:41539755 SUPPORT Other
"Yersinia enterocolitica, a major foodborne zoonotic pathogen with the capabilities of biofilm formation and psychrotolerance, poses critical risks to food transportation and cold-chain safety."
The study supports cold-chain persistence as a food-safety exposure context for Y. enterocolitica.
Mechanism Target:
PREDISPOSES Pork-Borne Yersinia enterocolitica Ingestion — Cold-chain survival and food-processing biofilms amplify contamination before the contaminated food is swallowed.
Show evidence (2 references)
PMID:41539755 SUPPORT Other
"Yersinia enterocolitica, a major foodborne zoonotic pathogen with the capabilities of biofilm formation and psychrotolerance, poses critical risks to food transportation and cold-chain safety."
The food-chain survey links biofilm formation and psychrotolerance to persistence during transport and cold-chain handling.
PMID:26403101 SUPPORT INDIRECT REVIEW SYNTHESIS Other
"Y. enterocolitica, as a typical psychrophil, multiplies in a food (neutral pH, stored at 5 °C) from 10/mL to 2.8 × 107/mL in 5 days"
The review describes low-temperature bacterial multiplication in food as the intermediate that can maintain or amplify infectious inocula.
Cold-stored red blood cell contamination
Y. enterocolitica can proliferate in refrigerated red blood cell concentrates, making contaminated transfusion products a rare but severe route to systemic yersiniosis.
Show evidence (1 reference)
PMID:33341965 SUPPORT BACKGROUND In Vitro
"Red blood cell concentrates (RBCC) are susceptible to bacterial contamination despite cold storage."
The transfusion-reference-strain study establishes that cold-stored red blood cell products remain vulnerable to bacterial contamination.
Mechanism Target:
TRIGGERS Cold-Stored Blood Product Yersinia Inoculation — Transfusion of a contaminated red-blood-cell unit bypasses intestinal acquisition and inoculates cold-amplified organisms into the bloodstream.
Show evidence (1 reference)
PMID:33341965 SUPPORT In Vitro
"two Y. enterocolitica strains reached the stationary phase between days 14 and 21 of RBCC storage with a bacterial concentration of approximately 109 CFU/ml."
Growth in red blood cell concentrates explains how rare contamination can amplify during cold blood-bank storage.
🔬

Diagnosis

2
Stool culture with cold enrichment and pathogenic-biotype identification
Isolation on Yersinia-selective media with cold enrichment, CR-MOX phenotype testing, biochemical tests, serotyping, and sequencing can separate pathogenic bioserotypes from Y. enterocolitica-like species.
Show evidence (2 references)
PMID:19219471 SUPPORT Human Clinical
"The cold-enrichment increased the number of all isolates, and 25% of the bio/serotype 4/O:3 and 2/O:9 strains were only found by cold-enrichment."
The clinical-stool study supports cold enrichment as a sensitivity step for detecting pathogenic bio/serotypes.
PMID:19219471 SUPPORT Human Clinical
"The microscopic colony identification on CIN agar with positive CR-MOX test, combined with several biochemical tests, identified reliably the pathogenic YE bioserotypes"
CIN morphology, CR-MOX testing, and biochemical profiling are supported as a diagnostic workflow for pathogenic Y. enterocolitica bioserotypes.
Quadruplex real-time qPCR patho-serotyping
Two-group quadruplex RT-qPCR can detect pathogenic O-serotypes and virulence markers for molecular identification, source attribution, and epidemiologic monitoring.
Show evidence (1 reference)
PMID:40445798 SUPPORT In Vitro
"We present a two-group quadruplex real-time quantitative PCR (RT-qPCR) for the patho-serotyping of Y. enterocolitica."
The assay paper directly describes a quadruplex real-time PCR for molecular patho-serotyping of Y. enterocolitica.
📈

Progression

3
Acute enterocolitis and pseudoappendicitis
Most symptomatic disease is localized to the intestine and regional mesenteric lymph nodes, producing enteritis or terminal-ileitis pseudoappendicitis.
Show evidence (1 reference)
PMID:15254824 SUPPORT REVIEW SYNTHESIS Other
"Intestinal yersiniosis may manifest in humans as (1) enteritis, (2) terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3) septicemia leading to focal abscesses in spleen and liver."
The review distinguishes localized enteritis and terminal ileitis with mesenteric adenitis from disseminated septicemia.
Iron-potentiated septicemia
Iron overload or deferoxamine therapy can shift infection toward invasive septicemia because ferrioxamine can supply iron for systemic bacterial growth.
Show evidence (1 reference)
PMID:12019084 SUPPORT Model Organism
"In a mouse experimental model of infection, the 50% lethal dose (LD(50)) of strain IP864 was decreased by more than 5 log units in mice pretreated with deferoxamine, while a deferiprone pretreatment did not affect it."
Deferoxamine potentiated Y. enterocolitica virulence in vivo, supporting the iron-chelator branch toward systemic infection.
Post-enteric reactive arthritis
A subset of patients develops sterile asymmetric oligoarthritis several days to weeks after the gastrointestinal infection.
Show evidence (1 reference)
PMID:40473988 SUPPORT REVIEW SYNTHESIS Other
"Reactive arthritis, initially described at the beginning of the twentieth century, is characterized by a sterile articular inflammation occurring several days to weeks after a bacterial gastrointestinal or urogenital infection."
The review supports the delayed post-enteric timing and sterile inflammatory nature of reactive arthritis.
📊

Prevalence

1
Reported non-pestis yersiniosis, United States, 2016-2023
Unknown Unknown
Non-pestis yersiniosis had the largest reported-incidence increase among bacterial enteric infections in the United States from 2016 to 2023. This is a qualitative surveillance trend, not a denominator-based annual incidence estimate.
Show evidence (1 reference)
PMID:42720049 SUPPORT Human Clinical
"non-pestis yersiniosis experienced the largest increase in reported incidence of any bacterial enteric infection in the United States during 2016-2023"
The outbreak review establishes the recent United States incidence trend for non-pestis yersiniosis.
🦠

Infectious Agent

1
Yersinia enterocolitica
Human yersiniosis is caused by pathogenic Y. enterocolitica biotypes that combine chromosomal virulence genes with the pYV virulence plasmid encoding YadA and the Ysc-Yop type III secretion system.
Yersinia enterocolitica NCBITaxon:630 NCBI Taxonomy (NCBITaxon)
Show evidence (2 references)
PMID:26403101 SUPPORT REVIEW SYNTHESIS Other
"INTRODUCTION: Y. enterocolitica is the causative agent of yersiniosis - a foodborne zoonosis with substantial importance to public health."
The review identifies Y. enterocolitica as the bacterial cause of yersiniosis.
PMID:28400007 SUPPORT In Vitro
"The virulence of the strains belonging to biotypes 1B and 2-5 depends on the presence of both chromosomal and plasmid-borne genes."
The molecular survey supports modeling pathogenic Y. enterocolitica as requiring both chromosomal and plasmid-encoded virulence functions.
↔️

Transmission

1
Pork-associated foodborne zoonotic transmission
Human infection is commonly acquired by eating raw, undercooked, or otherwise contaminated pork from pigs that carry pathogenic Y. enterocolitica in tonsillar tissue at slaughter.
Show evidence (2 references)
PMID:26403101 SUPPORT REVIEW SYNTHESIS Other
"Swine play an important role as a reservoir of Y. enterocolitica and insufficiently thermally processed pork is the main source of infection to humans."
The review supports swine as a reservoir and undercooked pork as a major exposure vehicle.
PMID:29307129 SUPPORT Other
"Yersinia enterocolitica causes foodborne disease in humans and infections are usually acquired from contaminated raw or undercooked pork. Pigs are considered the primary reservoir of human pathogenic bio-serotypes."
Swine tonsil surveillance supports the reservoir and raw/undercooked pork transmission route.
🐁

Animal Models

3
Oral Yersinia enterocolitica mouse infection
Oral mouse infection with Y. enterocolitica is used to assay intestinal colonization severity and the protective contribution of adoptively transferred innate lymphoid cell subsets.
Species
Mus musculus
Genotype
Wild-type or immune-deficient recipient mice
Publication
PMID:32147792
Pathograph links
Invasin-Mediated Peyer's Patch Entry partially recapitulates fidelity: moderate observes: organism The model uses oral infection to capture the intestinal entry context in which Peyer's patch invasion and mucosal innate lymphoid responses are measured.
Limitations: The method focuses on mouse intestinal infection and innate lymphoid cell transfers rather than on a complete human foodborne outbreak exposure.
Show evidence (1 reference)
PMID:32147792 SUPPORT Model Organism
"Here, we describe a mouse model of oral infection by Yersinia enterocolitica (Y. enterocolitica) and several different methodologies to assess the severity of the infection."
The methods article describes oral Y. enterocolitica infection in mice as a model for assaying enteric infection severity.
Rodent yersiniosis model
Rodent infection is used to follow Y. enterocolitica entry across Peyer's patches, dissemination to lymph nodes and reticuloendothelial organs, focal lesions, and immune-cell requirements for host defense.
Species
Rodents
Publication
PMID:8363822
Pathograph links
Phagocyte-Associated Mesenteric Dissemination recapitulates fidelity: moderate observes: organism Mouse and rabbit infection reproduce Peyer's-patch entry and downstream spread into lymph nodes, spleen, and liver, while rat infection can model the post-infectious arthritis branch.
Limitations: The review spans mice, rabbits, and rats because no single rodent model recapitulates every intestinal and post-infectious manifestation.
Show evidence (1 reference)
PMID:8363822 SUPPORT REVIEW SYNTHESIS Other
"experimental Y. enterocolitica infection in rodents resembles yersiniosis in humans and thus offers extraordinary opportunities to study the sequential steps of the infectious process."
The review supports rodent infection as a model for sequential human yersiniosis steps.
Ye WAP-314-infected C57BL/6 mouse
Infection of C57BL/6 mice with the Y. enterocolitica WAP-314 O:8 strain is used to measure myeloid-derived suppressor cell expansion in the spleen, mesenteric lymph nodes, and intestinal mucosa.
Species
Mus musculus
Genotype
C57BL/6 wild-type
Publication
PMID:39529636
Pathograph links
YopJ-Driven Macrophage Survival-Pathway Blockade partially recapitulates fidelity: moderate observes: organism The model measures a downstream anti-inflammatory myeloid response to infection in the same mesenteric and splenic compartments seeded by invasive Y. enterocolitica.
Limitations: The experiment reads out suppressive myeloid-cell expansion rather than directly perturbing YopJ activity.
Show evidence (1 reference)
PMID:39529636 SUPPORT Model Organism
"C57BL/6 wild-type mice were infected with Ye WAP-314 serotype O:8."
The paper directly identifies the Y. enterocolitica-infected mouse model used to assay myeloid-derived suppressor responses.
{ }

Source YAML

click to show 
name: Yersinia Enterocolitica Infectious Disease
creation_date: '2026-09-27T21:14:43Z'
category: Infectious Disease
description: >-
  Yersinia enterocolitica infectious disease is a foodborne zoonotic infection
  in which ingestion of Yersinia enterocolitica from contaminated pork or other
  vehicles leads to invasive ileal enterocolitis, mesenteric lymphadenitis, and
  pseudoappendicitis, with septicemia and focal hepatic or splenic abscesses in
  vulnerable iron-overloaded or immunocompromised hosts.
disease_term:
  preferred_term: Yersinia enterocolitica infectious disease
  term:
    id: MONDO:0042370
    label: Yersinia enterocolitica infectious disease
parents:
- Yersinia infectious disease
- Bacterial enteritis
synonyms:
- Yersinia enterocolitica infection
- intestinal yersiniosis
- yersiniosis
definitions:
- name: Intestinal yersiniosis clinical spectrum
  definition_type: CASE_DEFINITION
  description: >-
    Intestinal yersiniosis spans enteritis, terminal ileitis with mesenteric
    lymphadenitis or pseudoappendicitis, and septicemic disease with splenic or
    hepatic abscesses.
  evidence:
  - reference: PMID:15254824
    reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Intestinal yersiniosis may manifest in humans as (1) enteritis, (2)
      terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3)
      septicemia leading to focal abscesses in spleen and liver.
    explanation: >-
      The review defines the major enteric, pseudoappendiceal, and septicemic
      clinical forms captured by this disease entry.
infectious_agent:
- name: Yersinia enterocolitica
  infectious_agent_term:
    preferred_term: Yersinia enterocolitica
    term:
      id: NCBITaxon:630
      label: Yersinia enterocolitica
  description: >-
    Human yersiniosis is caused by pathogenic Y. enterocolitica biotypes that
    combine chromosomal virulence genes with the pYV virulence plasmid encoding
    YadA and the Ysc-Yop type III secretion system.
  evidence:
  - reference: PMID:26403101
    reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      INTRODUCTION: Y. enterocolitica is the causative agent of yersiniosis - a
      foodborne zoonosis with substantial importance to public health.
    explanation: >-
      The review identifies Y. enterocolitica as the bacterial cause of
      yersiniosis.
  - reference: PMID:28400007
    reference_title: Evaluation of virulence genes in Yersinia enterocolitica strains using SYBR Green real-time PCR.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The virulence of the strains belonging to biotypes 1B and 2-5 depends on
      the presence of both chromosomal and plasmid-borne genes.
    explanation: >-
      The molecular survey supports modeling pathogenic Y. enterocolitica as
      requiring both chromosomal and plasmid-encoded virulence functions.
transmission:
- name: Pork-associated foodborne zoonotic transmission
  description: >-
    Human infection is commonly acquired by eating raw, undercooked, or
    otherwise contaminated pork from pigs that carry pathogenic Y.
    enterocolitica in tonsillar tissue at slaughter.
  evidence:
  - reference: PMID:26403101
    reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Swine play an important role as a reservoir of Y. enterocolitica and
      insufficiently thermally processed pork is the main source of infection to
      humans.
    explanation: >-
      The review supports swine as a reservoir and undercooked pork as a major
      exposure vehicle.
  - reference: PMID:29307129
    reference_title: Identification and characterization of Yersinia enterocolitica strains isolated from pig tonsils at slaughterhouse in Central Italy.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Yersinia enterocolitica causes foodborne disease in humans and infections
      are usually acquired from contaminated raw or undercooked pork. Pigs are
      considered the primary reservoir of human pathogenic bio-serotypes.
    explanation: >-
      Swine tonsil surveillance supports the reservoir and raw/undercooked pork
      transmission route.
progression:
- phase: Acute enterocolitis and pseudoappendicitis
  notes: >-
    Most symptomatic disease is localized to the intestine and regional
    mesenteric lymph nodes, producing enteritis or terminal-ileitis
    pseudoappendicitis.
  evidence:
  - reference: PMID:15254824
    reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Intestinal yersiniosis may manifest in humans as (1) enteritis, (2)
      terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3)
      septicemia leading to focal abscesses in spleen and liver.
    explanation: >-
      The review distinguishes localized enteritis and terminal ileitis with
      mesenteric adenitis from disseminated septicemia.
- phase: Iron-potentiated septicemia
  notes: >-
    Iron overload or deferoxamine therapy can shift infection toward invasive
    septicemia because ferrioxamine can supply iron for systemic bacterial
    growth.
  evidence:
  - reference: PMID:12019084
    reference_title: Comparison of the effects of deferiprone versus deferoxamine on growth and virulence of Yersinia enterocolitica.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      In a mouse experimental model of infection, the 50% lethal dose (LD(50))
      of strain IP864 was decreased by more than 5 log units in mice pretreated
      with deferoxamine, while a deferiprone pretreatment did not affect it.
    explanation: >-
      Deferoxamine potentiated Y. enterocolitica virulence in vivo, supporting
      the iron-chelator branch toward systemic infection.
- phase: Post-enteric reactive arthritis
  notes: >-
    A subset of patients develops sterile asymmetric oligoarthritis several days
    to weeks after the gastrointestinal infection.
  evidence:
  - reference: PMID:40473988
    reference_title: "Reactive arthritis: a comprehensive journey through diagnostic findings."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Reactive arthritis, initially described at the beginning of the twentieth
      century, is characterized by a sterile articular inflammation occurring
      several days to weeks after a bacterial gastrointestinal or urogenital
      infection.
    explanation: >-
      The review supports the delayed post-enteric timing and sterile
      inflammatory nature of reactive arthritis.
prevalence:
- population: Reported non-pestis yersiniosis, United States, 2016-2023
  measure_type: UNKNOWN
  prevalence_class: UNKNOWN
  notes: >-
    Non-pestis yersiniosis had the largest reported-incidence increase among
    bacterial enteric infections in the United States from 2016 to 2023. This
    is a qualitative surveillance trend, not a denominator-based annual
    incidence estimate.
  evidence:
  - reference: PMID:42720049
    reference_title: "Fifty Years of Non-pestis Yersinia Outbreaks in the United States: Patterns, Vehicles, and Surveillance Challenges, 1971-2024."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      non-pestis yersiniosis experienced the largest increase in reported
      incidence of any bacterial enteric infection in the United States during
      2016-2023
    explanation: >-
      The outbreak review establishes the recent United States incidence trend
      for non-pestis yersiniosis.
genetic:
- name: HLA-B27
  relationship_type: SUSCEPTIBILITY
  association: HLA-B27 predisposes to Yersinia enterocolitica-associated reactive arthritis
  evidence:
  - reference: PMID:7221767
    reference_title: Yersinia arthritis mimicking acute rheumatic fever. A case report.
    supports: SUPPORT
    quote_role: BACKGROUND
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A reactive or post-infectious arthritis is a well-known complication of
      yersinia enterocolitica infection and tends to occur in patients with the
      HLA-B27 haplotype.
    explanation: >-
      The case-report background identifies HLA-B27 as a host haplotype
      associated with the post-infectious arthritis complication of Y.
      enterocolitica.
environmental:
- name: Pork and dairy food exposure
  description: >-
    Pork and dairy products are repeatedly implicated food vehicles for
    non-pestis Yersinia outbreaks, with raw or undercooked pork providing the
    central route from the swine reservoir to human intestinal exposure.
  influences_mechanisms:
  - target: Pork-Borne Yersinia enterocolitica Ingestion
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Consumption of contaminated pork or dairy delivers viable Y.
      enterocolitica to the intestine.
    evidence:
    - reference: PMID:26403101
      reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
      supports: SUPPORT
      quote_role: REVIEW_SYNTHESIS
      evidence_source: OTHER
      snippet: >-
        Swine play an important role as a reservoir of Y. enterocolitica and
        insufficiently thermally processed pork is the main source of infection
        to humans.
      explanation: >-
        The review supports undercooked pork as a major exposure route for
        human ingestion of Y. enterocolitica.
    - reference: PMID:42720049
      reference_title: "Fifty Years of Non-pestis Yersinia Outbreaks in the United States: Patterns, Vehicles, and Surveillance Challenges, 1971-2024."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Pork (46%) and dairy (18%) products were the most frequently identified
        food vehicles
      explanation: >-
        The outbreak review identifies pork and dairy as the most common food
        vehicles in United States non-pestis Yersinia outbreaks.
  evidence:
  - reference: PMID:42720049
    reference_title: "Fifty Years of Non-pestis Yersinia Outbreaks in the United States: Patterns, Vehicles, and Surveillance Challenges, 1971-2024."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pork (46%) and dairy (18%) products were the most frequently identified
      food vehicles
    explanation: >-
      Pork and dairy were the leading outbreak vehicles in the United States
      non-pestis Yersinia outbreak review.
  - reference: PMID:29307129
    reference_title: Identification and characterization of Yersinia enterocolitica strains isolated from pig tonsils at slaughterhouse in Central Italy.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Yersinia enterocolitica was isolated from 35 out of 376 (9.31%) samples.
    explanation: >-
      The slaughterhouse survey quantifies Y. enterocolitica tonsillar carriage
      in pigs, supporting the food-animal reservoir rather than human disease
      prevalence.
- name: Cold-chain persistence and food-processing contamination
  description: >-
    Psychrotolerance and biofilm formation let Y. enterocolitica persist across
    refrigerated food-processing and retail settings, increasing the chance
    that contaminated food remains infectious at consumption.
  influences_mechanisms:
  - target: Pork-Borne Yersinia enterocolitica Ingestion
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Cold-chain survival and food-processing biofilms amplify contamination
      before the contaminated food is swallowed.
    evidence:
    - reference: PMID:41539755
      reference_title: "Deciphering the potential risks of Yersinia enterocolitica across multi-points in food chain: prevalence, biofilm, and cross-stage transmission routes."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Yersinia enterocolitica, a major foodborne zoonotic pathogen with the
        capabilities of biofilm formation and psychrotolerance, poses critical
        risks to food transportation and cold-chain safety.
      explanation: >-
        The food-chain survey links biofilm formation and psychrotolerance to
        persistence during transport and cold-chain handling.
    - reference: PMID:26403101
      reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
      supports: SUPPORT
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      evidence_source: OTHER
      snippet: >-
        Y. enterocolitica, as a typical psychrophil, multiplies in a food
        (neutral pH, stored at 5 °C) from 10/mL to 2.8 × 107/mL in 5 days
      explanation: >-
        The review describes low-temperature bacterial multiplication in food as
        the intermediate that can maintain or amplify infectious inocula.
  evidence:
  - reference: PMID:41539755
    reference_title: "Deciphering the potential risks of Yersinia enterocolitica across multi-points in food chain: prevalence, biofilm, and cross-stage transmission routes."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Yersinia enterocolitica, a major foodborne zoonotic pathogen with the
      capabilities of biofilm formation and psychrotolerance, poses critical
      risks to food transportation and cold-chain safety.
    explanation: >-
      The study supports cold-chain persistence as a food-safety exposure
      context for Y. enterocolitica.
- name: Cold-stored red blood cell contamination
  description: >-
    Y. enterocolitica can proliferate in refrigerated red blood cell
    concentrates, making contaminated transfusion products a rare but severe
    route to systemic yersiniosis.
  influences_mechanisms:
  - target: Cold-Stored Blood Product Yersinia Inoculation
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Transfusion of a contaminated red-blood-cell unit bypasses intestinal
      acquisition and inoculates cold-amplified organisms into the bloodstream.
    evidence:
    - reference: PMID:33341965
      reference_title: Establishment of transfusion-relevant bacteria reference strains for red blood cells.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        two Y. enterocolitica strains reached the stationary phase between days
        14 and 21 of RBCC storage with a bacterial concentration of approximately
        109  CFU/ml.
      explanation: >-
        Growth in red blood cell concentrates explains how rare contamination
        can amplify during cold blood-bank storage.
  evidence:
  - reference: PMID:33341965
    reference_title: Establishment of transfusion-relevant bacteria reference strains for red blood cells.
    supports: SUPPORT
    quote_role: BACKGROUND
    evidence_source: IN_VITRO
    snippet: >-
      Red blood cell concentrates (RBCC) are susceptible to bacterial
      contamination despite cold storage.
    explanation: >-
      The transfusion-reference-strain study establishes that cold-stored red
      blood cell products remain vulnerable to bacterial contamination.
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
    evidence:
    - reference: PMID:26403101
      reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
      supports: SUPPORT
      quote_role: REVIEW_SYNTHESIS
      evidence_source: OTHER
      snippet: >-
        INTRODUCTION: Y. enterocolitica is the causative agent of yersiniosis -
        a foodborne zoonosis with substantial importance to public health.
      explanation: >-
        Yersiniosis is an acquired bacterial zoonosis, placing it in Harrison's
        Infectious Diseases Part.
pathophysiology:
- name: Pork-Borne Yersinia enterocolitica Ingestion
  description: >-
    Infection starts when viable pathogenic Y. enterocolitica reaches the small
    intestine after ingestion of contaminated raw or undercooked pork or another
    fecally contaminated vehicle.
  downstream:
  - target: Invasin-Mediated Peyer's Patch Entry
    description: >-
      Enteric delivery positions bacteria at the follicle-associated epithelium
      over Peyer's patches for M-cell translocation.
    evidence:
    - reference: PMID:27107739
      reference_title: Mononuclear phagocytes contribute to intestinal invasion and dissemination of Yersinia enterocolitica.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        After colonisation of the small intestine Ye invades the Peyer's patches
        (PPs) via M cells and disseminates to the mesenteric lymph nodes (MLNs),
        spleen and liver.
      explanation: >-
        Oral mouse infection shows that small-intestinal colonization precedes
        Peyer's-patch invasion and deeper spread.
  - target: YstA Heat-Stable Enterotoxin Secretion
    description: >-
      Pathogenic organisms entering the intestinal lumen can express the
      chromosomally encoded YstA enterotoxin branch that contributes to acute
      diarrheal enteritis.
    evidence:
    - reference: PMID:28400007
      reference_title: Evaluation of virulence genes in Yersinia enterocolitica strains using SYBR Green real-time PCR.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        The most common virulence-associated gene in pathogenic Y.
        enterocolitica proved to be ystA
      explanation: >-
        Virulence-gene screening supports ystA as a common marker of pathogenic
        Y. enterocolitica biotypes.
  evidence:
  - reference: PMID:26403101
    reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Swine play an important role as a reservoir of Y. enterocolitica and
      insufficiently thermally processed pork is the main source of infection to
      humans.
    explanation: >-
      The review supports contaminated pork ingestion as a major initiating
      exposure for human yersiniosis.
- name: Invasin-Mediated Peyer's Patch Entry
  description: >-
    Yersinia invasin binds host beta-1 integrins on intestinal epithelial and M
    cells, enabling internalization across the ileal mucosa and entry into
    Peyer's patch lymphoid tissue.
  locations:
  - preferred_term: small intestine Peyer's patch
    term:
      id: UBERON:0003454
      label: small intestine Peyer's patch
  cell_types:
  - preferred_term: M cell of gut
    term:
      id: CL:0000682
      label: M cell of gut
  biological_processes:
  - preferred_term: symbiont entry into host cell
    term:
      id: GO:0046718
      label: symbiont entry into host cell
  downstream:
  - target: Phagocyte-Associated Mesenteric Dissemination
    description: >-
      Organisms entering across Peyer's patches and lamina propria are carried
      by mononuclear phagocytes toward mesenteric lymph nodes and, in severe
      infection, deeper reticuloendothelial sites.
    evidence:
    - reference: PMID:27107739
      reference_title: Mononuclear phagocytes contribute to intestinal invasion and dissemination of Yersinia enterocolitica.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Altogether, MCs and CD103(+) DCs contribute to immediate invasion and
        dissemination of Ye.
      explanation: >-
        The mouse infection study supports monocyte-derived cells and dendritic
        cells as contributors to early bacterial dissemination.
  evidence:
  - reference: PMID:26731748
    reference_title: Hypoxia Decreases Invasin-Mediated Yersinia enterocolitica Internalization into Caco-2 Cells.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      These bacteria can cross the intestinal mucosa, and invade eukaryotic cells
      by binding to host β1 integrins, a process mediated by the bacterial
      effector protein invasin.
    explanation: >-
      Intestinal epithelial-cell assays support beta-1 integrin binding by
      invasin as a host-entry mechanism.
- name: Phagocyte-Associated Mesenteric Dissemination
  description: >-
    After mucosal entry, Y. enterocolitica can associate with CD103-positive
    dendritic cells and monocyte-derived cells in the lamina propria and spread
    to mesenteric lymph nodes, spleen, and liver.
  cell_types:
  - preferred_term: dendritic cell
    term:
      id: CL:0000451
      label: dendritic cell
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  locations:
  - preferred_term: mesenteric lymph node
    term:
      id: UBERON:0002509
      label: mesenteric lymph node
  downstream:
  - target: pYV Type III Secretion and Yop Effector Injection
    description: >-
      Disseminating pathogenic organisms use the pYV-encoded type III secretion
      apparatus to deliver anti-host Yop proteins into interacting phagocytes.
    evidence:
    - reference: PMID:8709853
      reference_title: "Mutational analysis of the Yersinia enterocolitica virC operon: characterization of yscE, F, G, I, J, K required for Yop secretion and yscH encoding YopR."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Pathogenic yersiniae secrete the Yop anti-host proteins using a type-III
        secretion pathway.
      explanation: >-
        The pYV virC mutational study establishes type III secretion as the
        export pathway for Yop anti-host proteins.
  - target: Deferoxamine-Potentiated Systemic Yersinia Replication
    description: >-
      Organisms that reach reticuloendothelial sites can cause septicemia and
      focal abscesses when iron overload or deferoxamine exposure permits
      systemic replication.
    evidence:
    - reference: PMID:15254824
      reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
      supports: SUPPORT
      quote_role: REVIEW_SYNTHESIS
      evidence_source: OTHER
      snippet: >-
        Intestinal yersiniosis may manifest in humans as (1) enteritis, (2)
        terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and
        (3) septicemia leading to focal abscesses in spleen and liver.
      explanation: >-
        The review links intestinal yersiniosis to severe septicemic spread into
        liver and spleen, the branch that deferoxamine can potentiate.
  evidence:
  - reference: PMID:27107739
    reference_title: Mononuclear phagocytes contribute to intestinal invasion and dissemination of Yersinia enterocolitica.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      After colonisation of the small intestine Ye invades the Peyer's patches
      (PPs) via M cells and disseminates to the mesenteric lymph nodes (MLNs),
      spleen and liver.
    explanation: >-
      Oral infection in mice supports spread from the small intestine to regional
      lymph nodes and systemic reticuloendothelial organs.
- name: Cold-Stored Blood Product Yersinia Inoculation
  description: >-
    Cold-stored red blood cell products can permit contaminating Y.
    enterocolitica to proliferate before transfusion-associated bloodstream
    inoculation.
  downstream:
  - target: Bacteremia
    description: >-
      Transfusion of a contaminated blood product can seed bacteria directly
      into the bloodstream and produce severe septic disease.
    evidence:
    - reference: PMID:26403101
      reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
      supports: SUPPORT
      quote_role: REVIEW_SYNTHESIS
      evidence_source: OTHER
      snippet: >-
        The septic form is also seen after the administration of blood, blood
        products or dialysis fluids stored at low temperature (4 C), in which Y.
        enterocolitica rods may grow.
      explanation: >-
        The review supports transfusion or dialysis fluids stored cold as a
        route to severe septic yersiniosis.
  evidence:
  - reference: PMID:33341965
    reference_title: Establishment of transfusion-relevant bacteria reference strains for red blood cells.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      two Y. enterocolitica strains reached the stationary phase between days 14
      and 21 of RBCC storage with a bacterial concentration of approximately 109
      CFU/ml.
    explanation: >-
      The ex-vivo blood-product study shows that Y. enterocolitica can
      proliferate during refrigerated red-blood-cell storage.
- name: pYV Type III Secretion and Yop Effector Injection
  description: >-
    Pathogenic Y. enterocolitica carries the pYV plasmid, whose Ysc secretion
    machinery exports Yop proteins into host immune cells.
  biological_processes:
  - preferred_term: protein secretion by the type III secretion system
    term:
      id: GO:0030254
      label: protein secretion by the type III secretion system
  downstream:
  - target: YopJ-Driven Macrophage Survival-Pathway Blockade
    description: >-
      Translocated YopJ/YopP blocks macrophage survival signaling and promotes
      death of innate immune cells.
    evidence:
    - reference: PMID:22563435
      reference_title: "YopJ-induced caspase-1 activation in Yersinia-infected macrophages: independent of apoptosis, linked to necrosis, dispensable for innate host defense."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        YopJ inhibits survival response pathways in macrophages, causing cell
        death.
      explanation: >-
        Macrophage infection experiments support YopJ-driven blockade of host
        survival pathways as a cell-death mechanism.
  evidence:
  - reference: PMID:8709853
    reference_title: "Mutational analysis of the Yersinia enterocolitica virC operon: characterization of yscE, F, G, I, J, K required for Yop secretion and yscH encoding YopR."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The components of the secretion machinery are encoded by three loci on the
      pYV plasmid: virA, virB, and virC.
    explanation: >-
      The mutational analysis maps the Yop type III secretion apparatus to the
      pYV virulence plasmid.
- name: YopJ-Driven Macrophage Survival-Pathway Blockade
  description: >-
    YopJ and related Yop effectors suppress macrophage survival and innate
    immune signaling, impairing bacterial clearance and amplifying ileal and
    mesenteric inflammation.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: effector-mediated suppression of host innate immune response
    term:
      id: GO:0140403
      label: effector-mediated suppression of host innate immune response
  - preferred_term: apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
  downstream:
  - target: Ileitis
    description: >-
      Anti-phagocyte Yop effector activity lets organisms persist in the ileal
      lymphoid tissue where terminal ileitis develops.
    evidence:
    - reference: PMID:8363822
      reference_title: "Experimental Yersinia enterocolitica infection in rodents: a model for human yersiniosis."
      supports: SUPPORT
      quote_role: REVIEW_SYNTHESIS
      evidence_source: OTHER
      snippet: >-
        experimental Y. enterocolitica infection in rodents resembles
        yersiniosis in humans and thus offers extraordinary opportunities to
        study the sequential steps of the infectious process.
      explanation: >-
        The animal-model review supports Yop-dependent rodent infection as a
        model of the sequential tissue steps leading to human intestinal
        yersiniosis.
  - target: Lymphadenitis
    description: >-
      Failed phagocyte clearance and Yop effector delivery support bacterial
      persistence in mesenteric lymph nodes.
    evidence:
    - reference: PMID:27107739
      reference_title: Mononuclear phagocytes contribute to intestinal invasion and dissemination of Yersinia enterocolitica.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        After colonisation of the small intestine Ye invades the Peyer's patches
        (PPs) via M cells and disseminates to the mesenteric lymph nodes (MLNs),
        spleen and liver.
      explanation: >-
        The oral infection model places mesenteric lymph-node dissemination
        downstream of intestinal invasion.
  evidence:
  - reference: PMID:22563435
    reference_title: "YopJ-induced caspase-1 activation in Yersinia-infected macrophages: independent of apoptosis, linked to necrosis, dispensable for innate host defense."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Yersinia outer protein J (YopJ) is a type III secretion system (T3SS)
      effector of pathogenic Yersinia (Yersinia pestis, Yersinia enterocolitica
      and Yersinia pseudotuberculosis) that is secreted into host cells.
    explanation: >-
      The paper identifies YopJ as a type III-secreted effector used by
      pathogenic Yersinia species, including Y. enterocolitica.
- name: Deferoxamine-Potentiated Systemic Yersinia Replication
  description: >-
    Deferoxamine provides chelated iron that pathogenic Y. enterocolitica can
    use under iron limitation, allowing invasive growth and septicemia in
    iron-overloaded hosts.
  chemical_entities:
  - preferred_term: deferoxamine
    term:
      id: CHEBI:4356
      label: desferrioxamine B
  - preferred_term: iron
    term:
      id: CHEBI:18248
      label: iron atom
  downstream:
  - target: Bacteremia
    description: >-
      Ferrioxamine-supported growth can amplify systemic organisms into
      Y. enterocolitica septicemia.
    evidence:
    - reference: PMID:12019084
      reference_title: Comparison of the effects of deferiprone versus deferoxamine on growth and virulence of Yersinia enterocolitica.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        the 50% lethal dose (LD(50)) of strain IP864 was decreased by more than
        5 log units in mice pretreated with deferoxamine
      explanation: >-
        Deferoxamine pretreatment sharply increased organismal virulence in the
        mouse infection model, supporting the severe systemic branch.
  - target: Splenic abscess
    description: >-
      Septicemic Y. enterocolitica can seed reticuloendothelial organs and form
      splenic abscesses.
    evidence:
    - reference: PMID:15254824
      reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
      supports: SUPPORT
      quote_role: REVIEW_SYNTHESIS
      evidence_source: OTHER
      snippet: >-
        septicemia leading to focal abscesses in spleen and liver
      explanation: >-
        The review explicitly links septicemia to focal splenic abscesses.
  - target: Liver abscess
    description: >-
      Septicemic Y. enterocolitica can seed reticuloendothelial organs and form
      hepatic abscesses.
    evidence:
    - reference: PMID:15254824
      reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
      supports: SUPPORT
      quote_role: REVIEW_SYNTHESIS
      evidence_source: OTHER
      snippet: >-
        septicemia leading to focal abscesses in spleen and liver
      explanation: >-
        The review explicitly links septicemia to focal liver abscesses.
  evidence:
  - reference: PMID:12019084
    reference_title: Comparison of the effects of deferiprone versus deferoxamine on growth and virulence of Yersinia enterocolitica.
    supports: SUPPORT
    quote_role: BACKGROUND
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Deferoxamine, a drug used to treat patients with iron overload, has the
      capacity to promote systemic Y. enterocolitica infections in humans.
    explanation: >-
      The deferoxamine study supports the clinical link between this iron
      chelator and systemic Y. enterocolitica infection.
- name: YstA Heat-Stable Enterotoxin Secretion
  description: >-
    Pathogenic Y. enterocolitica biotypes commonly carry ystA and can produce
    heat-stable enterotoxin independently of the pYV virulence plasmid,
    contributing a luminal toxin branch to acute diarrhea.
  downstream:
  - target: Diarrhea
    description: >-
      Heat-stable enterotoxin production in the intestinal lumen contributes to
      diarrheal enteritis during yersiniosis.
    evidence:
    - reference: PMID:26403101
      reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
      supports: SUPPORT
      quote_role: REVIEW_SYNTHESIS
      evidence_source: OTHER
      snippet: >-
        Yst enterotoxin (Yersinia-stable toxin) are produced as a result of myf
        and yst genes expression
      explanation: >-
        The review links yst genes to production of Yersinia-stable enterotoxin,
        the toxin branch upstream of diarrheal fluid secretion.
  evidence:
  - reference: PMID:28400007
    reference_title: Evaluation of virulence genes in Yersinia enterocolitica strains using SYBR Green real-time PCR.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The most common virulence-associated gene in pathogenic Y. enterocolitica
      proved to be ystA
    explanation: >-
      Virulence-gene screening identified ystA as a common marker of pathogenic
      Y. enterocolitica biotypes.
  - reference: PMID:30961808
    reference_title: Phenotypic and genotypic presence of the Yersinia virulence plasmid do not affect the production of enterotoxin YstA by Yersinia enterocolitica strains.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The results of this study indicate that the presence of pYV does not
      affect the enterotoxin-producing ability of Y. enterocolitica strains.
    explanation: >-
      The pig-isolate assay supports YstA enterotoxin production as an
      intestinal branch separable from the pYV type III secretion branch.
phenotypes:
- name: Diarrhea
  description: >-
    Acute enteric Y. enterocolitica infection can present as diarrheal
    enteritis.
  phenotype_term:
    preferred_term: Diarrhea
    term:
      id: HP:0002014
      label: Diarrhea
  evidence:
  - reference: PMID:26403101
    reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Yersiniosis usually appears with gastrointestinal disturbances in children,
      whereas in adults it manifests in a pseudo-appendix form.
    explanation: >-
      The review supports gastrointestinal disturbance as a common clinical
      manifestation of human yersiniosis.
- name: Fever
  description: Fever commonly accompanies symptomatic intestinal yersiniosis.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:26403101
    reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      gastroenterocolitis accompanied by fever and severe, often bloody,
      diarrhea
    explanation: >-
      The review lists fever among manifestations accompanying intestinal
      yersiniosis.
- name: Abdominal pain
  description: >-
    Abdominal pain accompanies the enterocolitis and pseudoappendiceal forms of
    symptomatic infection.
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:26403101
    reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Vomiting and abdominal pain lasting for 1-3 weeks are also observed
    explanation: >-
      The review lists abdominal pain among human yersiniosis manifestations.
- name: Ileitis
  description: >-
    Infection can involve the terminal ileum, producing an appendicitis-mimicking
    pseudoappendiceal syndrome.
  phenotype_term:
    preferred_term: Ileitis
    term:
      id: HP:0032564
      label: Ileitis
  evidence:
  - reference: PMID:15254824
    reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Intestinal yersiniosis may manifest in humans as (1) enteritis, (2)
      terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3)
      septicemia leading to focal abscesses in spleen and liver.
    explanation: >-
      The review explicitly lists terminal ileitis in the intestinal yersiniosis
      spectrum.
- name: Lymphadenitis
  description: >-
    Mesenteric lymphadenitis can accompany terminal ileitis and mimic acute
    appendicitis.
  phenotype_term:
    preferred_term: mesenteric lymphadenitis
    term:
      id: HP:0002840
      label: Lymphadenitis
  evidence:
  - reference: PMID:15254824
    reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Intestinal yersiniosis may manifest in humans as (1) enteritis, (2)
      terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3)
      septicemia leading to focal abscesses in spleen and liver.
    explanation: >-
      The review explicitly lists mesenteric lymphadenitis as part of the
      appendicitis-mimicking presentation.
- name: Bacteremia
  description: >-
    Severe invasive infection can disseminate to the bloodstream as septicemia.
  phenotype_term:
    preferred_term: Bacteremia
    term:
      id: HP:0031864
      label: Bacteremia
  evidence:
  - reference: PMID:15254824
    reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Intestinal yersiniosis may manifest in humans as (1) enteritis, (2)
      terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3)
      septicemia leading to focal abscesses in spleen and liver.
    explanation: >-
      Septicemia establishes bloodstream dissemination as a severe manifestation
      of intestinal yersiniosis.
- name: Splenic abscess
  description: >-
    Septicemic infection can seed the spleen and produce focal abscesses.
  phenotype_term:
    preferred_term: Splenic abscess
    term:
      id: HP:0025059
      label: Splenic abscess
  evidence:
  - reference: PMID:15254824
    reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      septicemia leading to focal abscesses in spleen and liver
    explanation: >-
      The review explicitly includes splenic abscesses in septicemic intestinal
      yersiniosis.
- name: Liver abscess
  description: >-
    Septicemic infection can seed the liver and produce focal abscesses.
  phenotype_term:
    preferred_term: Liver abscess
    term:
      id: HP:0100523
      label: Liver abscess
  evidence:
  - reference: PMID:15254824
    reference_title: "[Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and prevention]."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      septicemia leading to focal abscesses in spleen and liver
    explanation: >-
      The review explicitly includes hepatic abscesses in septicemic intestinal
      yersiniosis.
- name: Reactive arthritis
  description: >-
    Sterile inflammatory arthritis can develop days to weeks after the enteric
    infection.
  phenotype_term:
    preferred_term: reactive arthritis
    term:
      id: MONDO:0017376
      label: reactive arthritis
  evidence:
  - reference: PMID:40473988
    reference_title: "Reactive arthritis: a comprehensive journey through diagnostic findings."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      The most common agents include Chlamydia trachomatis, Ureaplasma
      urealyticum, and Neisseria gonorrhea for the venereal type and Salmonella
      enteriditis, Shigella flexneri, Yersinia enterocolitica for the
      post-enteric type.
    explanation: >-
      The review names Y. enterocolitica as a common post-enteric trigger of
      reactive arthritis.
- name: Erythema nodosum
  description: >-
    Y. enterocolitica infection can trigger erythema nodosum as an
    extraintestinal inflammatory manifestation.
  phenotype_term:
    preferred_term: Erythema nodosum
    term:
      id: HP:0012219
      label: Erythema nodosum
  evidence:
  - reference: PMID:26403101
    reference_title: Yersiniosis - a zoonotic foodborne disease of relevance to public health.
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      erythema nodosum, induced by Y. enterocolitica, constitutes over 20% of
      all erythema cases
    explanation: >-
      The review identifies erythema nodosum as a Y. enterocolitica-induced
      extraintestinal manifestation.
- name: Uveitis
  description: >-
    Uveitis is an extraintestinal manifestation within the broad reactive
    inflammatory spectrum of Y. enterocolitica infection.
  phenotype_term:
    preferred_term: Uveitis
    term:
      id: HP:0000554
      label: Uveitis
  evidence:
  - reference: PMID:8363822
    reference_title: "Experimental Yersinia enterocolitica infection in rodents: a model for human yersiniosis."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      Yersinia enterocolitica infection in humans causes a broad spectrum of
      diseases ranging from acute bowel disease to extraintestinal manifestations
      such as reactive arthritis, erythema nodosum and uveitis.
    explanation: >-
      The rodent-model review lists uveitis as an extraintestinal manifestation
      of human Y. enterocolitica infection.
diagnosis:
- name: Stool culture with cold enrichment and pathogenic-biotype identification
  description: >-
    Isolation on Yersinia-selective media with cold enrichment, CR-MOX
    phenotype testing, biochemical tests, serotyping, and sequencing can
    separate pathogenic bioserotypes from Y. enterocolitica-like species.
  evidence:
  - reference: PMID:19219471
    reference_title: "Yersinia enterocolitica and Y. enterocolitica-like species in clinical stool specimens of humans: identification and prevalence of bio/serotypes in Finland."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The cold-enrichment increased the number of all isolates, and 25% of the
      bio/serotype 4/O:3 and 2/O:9 strains were only found by cold-enrichment.
    explanation: >-
      The clinical-stool study supports cold enrichment as a sensitivity step
      for detecting pathogenic bio/serotypes.
  - reference: PMID:19219471
    reference_title: "Yersinia enterocolitica and Y. enterocolitica-like species in clinical stool specimens of humans: identification and prevalence of bio/serotypes in Finland."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The microscopic colony identification on CIN agar with positive CR-MOX
      test, combined with several biochemical tests, identified reliably the
      pathogenic YE bioserotypes
    explanation: >-
      CIN morphology, CR-MOX testing, and biochemical profiling are supported as
      a diagnostic workflow for pathogenic Y. enterocolitica bioserotypes.
- name: Quadruplex real-time qPCR patho-serotyping
  description: >-
    Two-group quadruplex RT-qPCR can detect pathogenic O-serotypes and virulence
    markers for molecular identification, source attribution, and epidemiologic
    monitoring.
  evidence:
  - reference: PMID:40445798
    reference_title: A two-group quadruplex real-time quantitative PCR assay for molecular patho-serotyping of Yersinia enterocolitica.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      We present a two-group quadruplex real-time quantitative PCR (RT-qPCR) for
      the patho-serotyping of Y. enterocolitica.
    explanation: >-
      The assay paper directly describes a quadruplex real-time PCR for
      molecular patho-serotyping of Y. enterocolitica.
animal_models:
- name: Oral Yersinia enterocolitica mouse infection
  species: Mus musculus
  genotype: Wild-type or immune-deficient recipient mice
  publication: PMID:32147792
  description: >-
    Oral mouse infection with Y. enterocolitica is used to assay intestinal
    colonization severity and the protective contribution of adoptively
    transferred innate lymphoid cell subsets.
  modeled_mechanisms:
  - target: Invasin-Mediated Peyer's Patch Entry
    relationship: PARTIALLY_RECAPITULATES
    fidelity: MODERATE
    model_scale: ORGANISM
    description: >-
      The model uses oral infection to capture the intestinal entry context in
      which Peyer's patch invasion and mucosal innate lymphoid responses are
      measured.
    limitations: >-
      The method focuses on mouse intestinal infection and innate lymphoid cell
      transfers rather than on a complete human foodborne outbreak exposure.
  evidence:
  - reference: PMID:32147792
    reference_title: Bacterial Infection Allows for Functional Examination of Adoptively Transferred Mouse Innate Lymphoid Cell Subsets.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Here, we describe a mouse model of oral infection by Yersinia
      enterocolitica (Y. enterocolitica) and several different methodologies to
      assess the severity of the infection.
    explanation: >-
      The methods article describes oral Y. enterocolitica infection in mice as
      a model for assaying enteric infection severity.
- name: Rodent yersiniosis model
  species: Rodents
  publication: PMID:8363822
  description: >-
    Rodent infection is used to follow Y. enterocolitica entry across Peyer's
    patches, dissemination to lymph nodes and reticuloendothelial organs, focal
    lesions, and immune-cell requirements for host defense.
  modeled_mechanisms:
  - target: Phagocyte-Associated Mesenteric Dissemination
    relationship: RECAPITULATES
    fidelity: MODERATE
    model_scale: ORGANISM
    description: >-
      Mouse and rabbit infection reproduce Peyer's-patch entry and downstream
      spread into lymph nodes, spleen, and liver, while rat infection can model
      the post-infectious arthritis branch.
    limitations: >-
      The review spans mice, rabbits, and rats because no single rodent model
      recapitulates every intestinal and post-infectious manifestation.
  evidence:
  - reference: PMID:8363822
    reference_title: "Experimental Yersinia enterocolitica infection in rodents: a model for human yersiniosis."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: >-
      experimental Y. enterocolitica infection in rodents resembles yersiniosis
      in humans and thus offers extraordinary opportunities to study the
      sequential steps of the infectious process.
    explanation: >-
      The review supports rodent infection as a model for sequential human
      yersiniosis steps.
- name: Ye WAP-314-infected C57BL/6 mouse
  species: Mus musculus
  genotype: C57BL/6 wild-type
  publication: PMID:39529636
  description: >-
    Infection of C57BL/6 mice with the Y. enterocolitica WAP-314 O:8 strain is
    used to measure myeloid-derived suppressor cell expansion in the spleen,
    mesenteric lymph nodes, and intestinal mucosa.
  modeled_mechanisms:
  - target: YopJ-Driven Macrophage Survival-Pathway Blockade
    relationship: PARTIALLY_RECAPITULATES
    fidelity: MODERATE
    model_scale: ORGANISM
    description: >-
      The model measures a downstream anti-inflammatory myeloid response to
      infection in the same mesenteric and splenic compartments seeded by
      invasive Y. enterocolitica.
    limitations: >-
      The experiment reads out suppressive myeloid-cell expansion rather than
      directly perturbing YopJ activity.
  evidence:
  - reference: PMID:39529636
    reference_title: Nitric oxide-producing monocyte-myeloid suppressor cells expand and accumulate in the spleen and mesenteric lymph nodes of Yersinia enterocolitica-infected mice.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      C57BL/6 wild-type mice were infected with Ye WAP-314 serotype O:8.
    explanation: >-
      The paper directly identifies the Y. enterocolitica-infected mouse model
      used to assay myeloid-derived suppressor responses.
treatments:
- name: Antibiotic therapy for invasive yersiniosis
  description: >-
    Third-generation cephalosporins, fluoroquinolones, and susceptibility-guided
    alternatives are used for severe invasive disease, while ampicillin and
    cefazolin are unreliable because clinical Y. enterocolitica strains are
    intrinsically resistant to those agents.
  treatment_term:
    preferred_term: antibiotic therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: ceftriaxone
      term:
        id: CHEBI:29007
        label: ceftriaxone
    - preferred_term: ciprofloxacin
      term:
        id: CHEBI:100241
        label: ciprofloxacin
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Phagocyte-Associated Mesenteric Dissemination
    treatment_effect: INHIBITS
    description: >-
      Active antibiotics reduce viable organisms responsible for systemic
      dissemination in invasive yersiniosis.
  - target: YstA Heat-Stable Enterotoxin Secretion
    treatment_effect: INHIBITS
    description: >-
      Active antibiotics reduce the viable enteric bacterial population that can
      produce YstA enterotoxin during symptomatic intestinal disease.
  evidence:
  - reference: PMID:10803262
    reference_title: "[Susceptibility to selected antibiotics of Yersinia enterocolitica 03 strains, carrying and not carrying plasmid pYV]."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Third-generation cephalosporins such as cefotaxime and ceftriaxone and a
      fluoroquinolone (ciprofloxacin) were the most active antimicrobial agents,
      tested followed by aztreonam, imipenem, trimethoprim, tetracycline,
      gentamicin, chloramphenicol, amoxycillin/clavulanate, cefaclor,
      cefuroxime, amikacin, furazolidone and sulphamethoxazole.
    explanation: >-
      Susceptibility testing of clinical serotype O:3 isolates supports
      third-generation cephalosporins and ciprofloxacin as active agents against
      Y. enterocolitica.
  - reference: PMID:10803262
    reference_title: "[Susceptibility to selected antibiotics of Yersinia enterocolitica 03 strains, carrying and not carrying plasmid pYV]."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Almost all tested strains were resistant to ampicillin and cefazolin
    explanation: >-
      The same clinical-isolate susceptibility series supports the intrinsic
      ampicillin and cefazolin resistance caveat in the treatment description.
📚

References & Deep Research

Deep Research

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Create: Yersinia Enterocolitica Infectious Disease · 2026-09-27T21:45:37Z · View source

Created the Yersinia enterocolitica infectious disease entry from an OpenScientist deep-research report, using MONDO:0042370 and NCBITaxon:630 as identity anchors. The entry captures pork-associated zoonotic transmission, the acute enteritis/terminal-ileitis/septicemia spectrum, invasin-mediated Peyer's-patch entry, mononuclear-phagocyte dissemination, pYV type III secretion with YopJ macrophage survival-pathway blockade, deferoxamine-potentiated systemic replication, core enteric and reactive-arthritis phenotypes, and antibiotic therapy for invasive disease. Refreshed the selected PubMed caches with just fetch-reference, verified 25/25 snippets, and reran just validate-disorders for the new YAML.

OpenScientist ▸
1. Disease Information
openscientist-autonomous 54 citations 2026-09-27T14:34:07.577931

1. Disease Information

Overview. Yersiniosis is an enteric infection caused by Yersinia enterocolitica, a Gram-negative, facultatively anaerobic, non-lactose-fermenting member of the Enterobacteriaceae. It is one of the more common causes of bacterial gastroenteritis in temperate regions and is notable for its psychrotolerance and its zoonotic, pork-associated transmission. Clinically it manifests along a spectrum from acute enteritis/enterocolitis to pseudoappendicitis and, in vulnerable hosts, septicemia (PMID: 15254824).

Key identifiers. MONDO:0042370; ICD-10 A04.6 (Enteritis due to Yersinia enterocolitica); ICD-11 1A03 (Enteritis due to Yersinia enterocolitica); MeSH D015008/D015009; causative organism NCBI:txid630.

Synonyms / alternative names. Yersiniosis; intestinal yersiniosis; Yersinia enterocolitica enteritis/enterocolitis; enteric yersiniosis; non-pestis yersiniosis.

Data provenance. This report aggregates disease-level evidence from primary literature, microbiological surveillance, case reports, meta-analysis, and experimental (rodent/in-vitro) studies rather than individual EHR records.

2. Etiology

Causal factor (infectious). The disease is caused by pathogenic bioserotypes of Y. enterocolitica. Globally, the principal human-pathogenic serotypes are O:3, O:9, O:8, and O:5,27, with bioserotype 4/O:3 dominant in most regions (PMID: 29307129, PMID: 40445798). Pigs are the primary reservoir; insufficiently cooked pork is the main vehicle (PMID: 26403101).

Environmental / exposure risk factors. Consumption of raw or undercooked pork (including chitterlings), unpasteurized dairy, and contaminated water; cold-chain storage that permits psychrotolerant growth; transfusion via contaminated blood products; occupational contact in the pork production chain. Young age is a risk factor for enterocolitis.

Host risk factors (the key modifier — iron). Iron overload and iron-chelation therapy with deferoxamine are the most important host risk factors for severe/invasive disease. In a mouse model, deferoxamine pretreatment decreased the LD₅₀ of Y. enterocolitica by >5 log units, whereas deferiprone did not (PMID: 12019084). Transfusion-dependent conditions (β-thalassemia, sickle cell disease) and dialysis iron supplementation predispose to fulminant infection (PMID: 31219970, PMID: 21266629, PMID: 11698009, PMID: 21151549). Diabetes, malignancy, and other immunocompromising conditions also predispose to bacteremia (PMID: 9376035).

Genetic host factor. HLA-B27 is a genetic susceptibility factor for the post-infectious complication of reactive arthritis (PMID: 7221767).

Protective factors. Thorough cooking of pork, pasteurization, cold-chain hygiene, and biosecurity reduce exposure. Mucosal innate defenses (e.g., Paneth-cell α-defensin HD6, which entraps enteric pathogens in self-assembled nanonets) limit invasion (PMID: 22722251). Use of the oral iron chelators deferiprone/deferasirox instead of deferoxamine avoids promoting bacterial growth (PMID: 12019084, PMID: 19413741).

Gene–environment interaction. The clearest interaction is iron availability × siderophore biology: exogenous ferrioxamine (from deferoxamine) supplies iron the bacterium cannot otherwise scavenge, converting a contained mucosal infection into systemic disease. A second interaction is HLA-B27 × enteric infection, where a genetically predisposed host mounts an aberrant post-infectious arthritic response.

3. Phenotypes

Phenotype Type Onset / course Frequency HPO suggestion
Diarrhea (often watery, sometimes bloody) Symptom Acute, self-limiting Very common in enterocolitis HP:0002014
Abdominal pain (right-lower-quadrant) Symptom Acute Common; prominent in pseudoappendicitis HP:0002027 / HP:0002574
Fever Sign Acute Common HP:0001945
Terminal ileitis / mesenteric lymphadenitis Clinical sign Subacute Older children/adults HP:0002583 (enterocolitis)
Pseudoappendicitis Clinical syndrome Acute Older children/young adults HP:0002605 (approximate)
Septicemia / bacteremia Lab/clinical Acute, severe Rare; iron-overloaded/immunocompromised HP:0100806
Hepatic/splenic abscesses Manifestation Invasive disease Rare HP:0012199 / HP:0020104
Reactive arthritis (asymmetric, lower-limb) Post-infectious Days–weeks after infection ~1/1000 (ReA overall); young adults 18–40 HP:0001369
Erythema nodosum Post-infectious skin sign Weeks after Occasional HP:0012219
Uveitis Post-infectious Weeks after Occasional HP:0000554
Graves' disease / autoimmune thyroiditis Post-infectious autoimmune Delayed Association (see §5) HP:0100647

Characteristics. Onset is typically acute; enterocolitis is generally self-limiting (1–3 weeks). Severity ranges from mild (children) to life-threatening (septicemia in iron overload). Post-infectious immunological syndromes are episodic/delayed (PMID: 8363822, PMID: 3545747).

Quality-of-life impact. Acute enterocolitis causes short-term disability from diarrhea/pain; pseudoappendicitis may lead to unnecessary appendectomy. Reactive arthritis and other post-infectious syndromes can cause prolonged joint pain and functional impairment persisting weeks to months (PMID: 32648451).

4. Genetic / Molecular Information

Yersiniosis is an infectious, not a Mendelian, disease; there are no causal human genes. The relevant genetics are (a) host susceptibility loci and (b) bacterial virulence genes.

Host genetics. HLA-B27 predisposes to post-infectious reactive arthritis (PMID: 7221767). No causal germline variants, chromosomal abnormalities, or pathogenic ACMG-classified variants apply to the disease itself. gnomAD/ClinVar entries are not applicable.

Bacterial virulence genetics. Pathogenicity of biotypes 1B and 2–5 depends on both chromosomal and pYV plasmid-borne genes; biotype 1A lacks pYV (PMID: 28400007).

  • Chromosomal: ail (attachment-invasion locus; principal chromosomal virulence marker — PMID: 28283072); inv (invasin); ystA (heat-stable enterotoxin YstA; best marker of pathogenic biotypes — PMID: 28400007); myfA (fimbriae); hreP (protease). Biotype 1A carries ystB and hreP but lacks ail/ystA (PMID: 39805396).
  • Plasmid (pYV, ~70 kb): virF/lcrF (master transcriptional activator of the T3SS regulon), yadA (adhesin), and the ysc operon encoding the T3SS (e.g., yscE, F, G, I, J, K, H) plus yop effector genes (PMID: 8709853). YstA enterotoxin production is pYV-independent (PMID: 30961808).

5. Environmental Information

Infectious agent. Yersinia enterocolitica (NCBI:txid630); a species divided into ~6 biotypes and ~60 O-serotypes, with O:3, O:9, O:8, O:5,27 principally associated with human disease (PMID: 40445798).

Environmental factors. The organism's psychrotolerance (growth at 4 °C) and biofilm formation enable persistence across refrigerated foods and food-processing environments; slaughterhouses (40.2%) and farmers' markets (34.8%) are high-risk contamination zones (PMID: 41539755). Contaminated red-blood-cell units support proliferation during cold storage, a recognized transfusion hazard (PMID: 33341965).

Lifestyle / dietary factors. Consumption of raw/undercooked pork (notably chitterlings), unpasteurized milk/dairy (18% of US outbreak vehicles), and untreated water (PMID: 42720049). Pork accounted for 46% of identified US outbreak vehicles.

Reservoirs. Swine are the primary reservoir (bioserotype 4/O:3); wildlife (badgers, roe deer, mustelids), poultry, and other livestock also carry the organism (PMID: 40582279, PMID: 41527869).

6. Mechanism / Pathophysiology

Ordered causal chain (initiating exposure → clinical manifestation)

  1. Ingestion of Y. enterocolitica in contaminated pork/dairy/water leads to delivery of viable bacteria to the small intestine (survival aided by psychrotolerance and acid tolerance).
  2. Bacteria colonize the terminal ileum; expression of chromosomal adhesins/invasins is favored at intestinal temperature/pH.
  3. Invasin binds host β1 integrins on the apical surface of M cells overlying Peyer's patches, resulting in receptor-mediated internalization and translocation across the follicle-associated epithelium (PMID: 27107739, PMID: 26731748). (Invasin is rapidly degraded by gut proteases, which limits the efficiency of this step — PMID: 21501502.)
  4. Uptake by lamina propria CD103⁺ dendritic cells and monocyte-derived phagocytes (invasin-dependent; YadA dispensable) leads to dissemination to mesenteric lymph nodes, and in some hosts the spleen and liver (PMID: 27107739).
  5. At 37 °C, the VirF/LcrF regulator induces the pYV-encoded T3SS, which upon host-cell contact injects Yop effectors (YopH, YopE, YopT, YopO, YopP/J, YopM) into phagocytes (PMID: 8709853).
  6. Yop effectors subvert innate immunity: YopH/E/T/O disrupt phagocytosis and actin dynamics; YopP/YopJ inhibits NF-κB/MAPK survival pathways, causing macrophage/DC apoptosis and modulating caspase-1/IL-1β (PMID: 22563435, PMID: 18559430). This results in immune evasion and local tissue inflammation → enterocolitis / terminal ileitis / mesenteric adenitis / pseudoappendicitis.
  7. YstA heat-stable enterotoxin activates guanylate cyclase in enterocytes, contributing to secretory diarrhea (PMID: 28400007, PMID: 30961808).

Branch A — host iron status → septicemia. Because Y. enterocolitica lacks a high-affinity siderophore, iron overload or deferoxamine therapy supplies chelated iron (ferrioxamine), which leads to unrestrained bacterial replication and systemic septicemia with hepatic/splenic abscesses (PMID: 12019084, PMID: 31219970).

Branch B — post-infectious autoimmunity. In HLA-B27⁺ hosts, enteric infection triggers reactive arthritis (PMID: 7221767). Independently, molecular mimicry between the bacterial outer-membrane porin OmpF (aa190–197) and a leucine-rich domain of the TSH receptor generates cross-reactive, thyroid-stimulating antibodies, contributing to Graves' disease / autoimmune thyroid disease (PMID: 20484489, PMID: 32564766).

Mechanistic categories

  • Molecular pathways: T3SS/Yop-mediated inhibition of NF-κB and MAPK signaling; modulation of the pyrin and caspase-1 inflammasomes (PMID: 31456795, PMID: 22563435); integrin/FAK signaling on invasion (PMID: 26731748). GO suggestions: GO:0030260 (entry into host cell), GO:0052031 (modulation by symbiont of host defense response), GO:0043123 (positive regulation of NF-κB signaling — inhibited).
  • Cellular processes: macrophage/DC apoptosis, inhibited phagocytosis, inflammation, MDSC-mediated immunosuppression (PMID: 39529636).
  • Protein dysfunction (host): Yop-driven dephosphorylation (YopH phosphatase) and cytoskeletal GTPase inactivation.
  • Immune involvement: ILC3-mediated mucosal protection (PMID: 32147792); neutrophils resist YopJ/P-induced apoptosis (PMID: 20174624); autoimmunity via mimicry (§5).
  • Cell types (CL): M cell (CL:0000682), dendritic cell (CL:0000451), macrophage (CL:0000235), neutrophil (CL:0000775), enterocyte (CL:0000584).
  • CHEBI entities: iron (CHEBI:18248), deferoxamine (CHEBI:4356), ferrioxamine B (CHEBI:87109).

7. Anatomical Structures Affected

  • Primary organs/systems (digestive): terminal ileum (UBERON:0002116), Peyer's patches (UBERON:0001211), mesenteric lymph nodes (UBERON:0002509), appendix/cecum region (pseudoappendicitis) (PMID: 15254824).
  • Secondary organ involvement: liver (UBERON:0002107) and spleen (UBERON:0002106) abscesses in septicemia; joints (reactive arthritis); skin (erythema nodosum); eye (uveitis); thyroid gland (Graves'); rarely heart (myopericarditis — PMID: 35728146) and inner ear/vestibular system (PMID: 9376035).
  • Tissue/cell level: intestinal follicle-associated epithelium and M cells; lymphoid tissue; mononuclear phagocytes.
  • Subcellular (GO cellular component): host plasma membrane / β1-integrin complex (GO:0008305); host cytoskeleton (targeted by Yops); bacterial T3SS injectisome.
  • Lateralization: reactive arthritis is characteristically asymmetric, lower-extremity oligoarthritis.

8. Temporal Development

  • Onset: acute, typically 4–7 days after ingestion; enterocolitis predominates in infants/young children, pseudoappendicitis in older children/young adults (PMID: 15254824).
  • Progression / duration: enterocolitis is usually self-limiting over 1–3 weeks; diarrhea can occasionally persist. Septicemia is acute and can be fulminant, especially with rapid decompensation after transfusion in iron-overloaded patients (PMID: 31219970).
  • Post-infectious window: reactive arthritis and erythema nodosum appear days to weeks after the enteric phase; autoimmune thyroid sequelae are more delayed.
  • Course pattern: acute self-limited enteric phase; post-infectious syndromes may be episodic/relapsing. Critical intervention windows: early antibiotics in high-risk (iron-overloaded/immunocompromised) hosts; avoidance of deferoxamine during suspected infection.

9. Inheritance and Population (Epidemiology)

  • Not heritable — infectious etiology; no Mendelian inheritance, penetrance, founder effects, or carrier frequency apply. Host susceptibility to sequelae is modulated by HLA-B27.
  • Incidence trend: non-pestis yersiniosis had the largest increase in reported incidence of any bacterial enteric infection in the US during 2016–2023 (PMID: 42720049).
  • Reservoir prevalence: Y. enterocolitica isolated from 9.31% of pig tonsils (bioserotype 4/O:3 = 95.74%) (PMID: 29307129); ~9.3% porcine tonsils and 3.3% pig faeces in other surveys (PMID: 19058737); ~9.3–9.7% prevalence in retail meats (PMID: 41527869, PMID: 40382034).
  • Geographic distribution: worldwide in temperate/cold climates; bioserotype 4/O:3 predominant in Europe/Asia; highly pathogenic 1B/O:8 historically North American but now reported in Iran (PMID: 40669762).
  • Age distribution: enterocolitis skews to young children (<5 years — PMID: 40669762); pseudoappendicitis to older children/young adults.
  • Seasonality: cold-season predominance consistent with psychrotolerance (PMID: 40669762).

10. Diagnostics

Culture (gold standard). Stool culture on CIN (cefsulodin–irgasan–novobiocin) agar with cold enrichment (4 °C) enhances recovery — cold enrichment recovered ~25% of 4/O:3 and 2/O:9 strains not otherwise detected (PMID: 19219471). Blood culture in suspected septicemia.

Bio/serotyping. Congo-red magnesium-oxalate (CR-MOX) agar detects the pYV virulence plasmid; biochemical panels assign biotype; agglutination/PCR serotyping identifies O:3, O:9, O:8, O:5,27 (PMID: 19219471, PMID: 40445798).

Molecular confirmation. PCR for virulence genes (ail, ystA/ystB, virF, yadA, inv, myfA) distinguishes pathogenic from non-pathogenic (biotype 1A) strains; 16S rRNA and gyrB sequencing resolves Y. enterocolitica-like species; multiplex/quadruplex RT-qPCR patho-serotyping is available (PMID: 19219471, PMID: 40445798).

Serology. Anti-Yersinia antibody titers (e.g., against O:3, O:9) support diagnosis of post-infectious syndromes such as reactive arthritis (PMID: 9376035). Caveat: O:9 cross-reacts serologically with Brucella.

Imaging. CT/ultrasound in pseudoappendicitis shows terminal ileitis and mesenteric lymphadenopathy (helping avoid unnecessary appendectomy).

Differential diagnosis. Acute appendicitis, Crohn's disease/terminal ileitis, Campylobacter/Salmonella/Shigella enterocolitis, mesenteric adenitis of other cause.

11. Outcome / Prognosis

  • Enterocolitis: excellent prognosis; usually self-limiting without antibiotics.
  • Pseudoappendicitis: favorable; risk of unnecessary surgery.
  • Septicemia: serious, with mortality concentrated in iron-overloaded/immunocompromised patients; requires prompt IV antibiotics (PMID: 21266629, PMID: 31219970). Case reports document successful treatment (e.g., 14-day ceftriaxone) with resolution and no recurrence.
  • Post-infectious morbidity: reactive arthritis (ReA overall prevalence ~1/1000) can cause weeks-to-months of joint disability (PMID: 40473988); persistent extraintestinal manifestations (uveitis, erythema nodosum, rare vestibular loss/myopericarditis) (PMID: 9376035, PMID: 35728146).
  • Prognostic factors: host iron status, immunocompetence, age, timeliness of antibiotic therapy, and infecting bioserotype (1B/O:8 highly pathogenic).

12. Treatment

General principle. Uncomplicated enterocolitis is self-limiting and generally does not require antibiotics; supportive care (rehydration) suffices. Antibiotics are indicated for invasive/septicemic disease and in high-risk hosts.

Antimicrobial susceptibility profile.

Antimicrobial class Susceptibility Evidence
Ampicillin, 1st-gen cephalosporins (cefazolin) Intrinsically RESISTANT (chromosomal β-lactamases blaA/blaB) PMID: 10803262, PMID: 10755244
3rd-gen cephalosporins (cefotaxime, ceftriaxone) Susceptible — drug of choice PMID: 10803262, PMID: 21266629
Fluoroquinolones (ciprofloxacin, ofloxacin) Susceptible; highly effective in models PMID: 10803262, PMID: 1952849
Aminoglycosides (gentamicin) Susceptible PMID: 10755244, PMID: 20828475
TMP-SMX, tetracyclines, chloramphenicol, imipenem, aztreonam Susceptible PMID: 10755244

Susceptibility is independent of the pYV plasmid (PMID: 10755244). In murine systemic infection, newer β-lactams may fail while fluoroquinolones (ofloxacin, 5 mg/kg) are very effective (PMID: 1952849).

Regimens. Septicemia is typically treated with a third-generation cephalosporin (e.g., ceftriaxone) ± an aminoglycoside or a fluoroquinolone; combination therapy is used for severe disease. NCIT term suggestions: Ceftriaxone (NCIT:C749), Ciprofloxacin (NCIT:C405), Gentamicin (NCIT:C557), Trimethoprim-Sulfamethoxazole (NCIT:C273).

Critical host management. In iron-overloaded patients, discontinue deferoxamine during infection and consider deferiprone/deferasirox, which do not promote bacterial growth (PMID: 12019084, PMID: 19413741).

AMR surveillance. Prudent antimicrobial use in pig farming is emphasized to limit resistance-gene spread via horizontal transfer (PMID: 41413462, PMID: 35369517).

Advanced/experimental therapeutics. Not applicable — no gene/cell/RNA/targeted therapies; treatment is antimicrobial and supportive.

13. Prevention

  • Primary prevention (food-chain hygiene — the mainstay): "Good hygienic slaughter practices are essential to prevent contamination of pork" (PMID: 19058737). Thorough cooking of pork, pasteurization of dairy, avoidance of cross-contamination, on-farm biosecurity, and cold-chain management from farm to fork (PMID: 40023561). Key on-farm risk factors to mitigate: batch mixing in fattening herds and poor pen cleaning/biosecurity (PMID: 19175574).
  • Immunization: No licensed human vaccine exists. Oral mucosal-vaccine constructs using Y. enterocolitica OmpH as a carrier are experimental (PMID: 32569608).
  • Secondary prevention: microbiological surveillance of the pork chain; molecular subtyping (SNP/MLST) to track transmission hotspots (slaughterhouses, markets) (PMID: 41539755).
  • Tertiary prevention: in iron-overloaded/dialysis patients, monitor ferritin, avoid deferoxamine when infection is suspected, and screen blood products (transfusion transmission hazard) (PMID: 21266629, PMID: 33341965).
  • Public health: food-safety education, blood-bank visual inspection/interdiction of contaminated RBC units.

14. Other Species / Natural Disease

  • Taxonomy of affected/reservoir species: Sus scrofa domesticus (pig; NCBI:txid9825) — primary reservoir; also cattle, sheep, poultry (chicken, duck), dogs, cats, and wildlife (badgers, roe deer, mustelids) (PMID: 40582279, PMID: 41527869).
  • Zoonotic transmission: fecal–oral via contaminated food, water, and animal contact; strong swine–human genomic link established by pangenome analysis (PMID: 41413462). Environmental persistence broadens the ecology.
  • Comparative pathology: pigs are typically asymptomatic carriers (tonsils, gut, mesenteric nodes), unlike humans who develop enteric disease — an important distinction for control.
  • Evolutionary conservation: T3SS/Yop virulence mechanisms are conserved across pathogenic Yersinia (Y. enterocolitica, Y. pseudotuberculosis, Y. pestis), enabling cross-species mechanistic inference (PMID: 18559430, PMID: 38271464).

15. Model Organisms

  • Rodent oral-infection models faithfully recapitulate human yersiniosis: "experimental Y. enterocolitica infection in rodents resembles yersiniosis in humans and thus offers extraordinary opportunities to study the sequential steps of the infectious process" (PMID: 8363822).
  • Mouse (C57BL/6): oral infection with serotype O:8 strains (WA-314, WAP-314) models Peyer's-patch/M-cell entry, ILC3-mediated protection (PMID: 32147792), NO-producing Mo-MDSC immunosuppression (PMID: 39529636), and bacterial population dynamics (PMID: 35205164). The deferoxamine-potentiation LD₅₀ experiment was performed in mice (PMID: 12019084).
  • Rabbit: models enterotoxin-mediated enteritis and humoral response (PMID: 8363822).
  • In vitro / cellular: Caco-2 intestinal epithelial cells for invasin–β1-integrin internalization (PMID: 26731748); primary macrophages/neutrophils for Yop-mediated apoptosis studies (PMID: 22563435, PMID: 20174624); suckling-mouse bioassay for YstA enterotoxin activity (PMID: 39805396).
  • Computational: ODE-based models of gastrointestinal bacterial population dynamics (PMID: 35205164).
  • Limitations: mouse strains used experimentally are often serotype O:8 (highly pathogenic 1B), which may not reflect the globally dominant 4/O:3; post-infectious autoimmune sequelae (Graves', HLA-B27 ReA) are not well captured in rodents.

Mechanistic Model / Integrated Interpretation

   Contaminated pork/dairy/water (psychrotolerant, biofilm)
     │  ingestion
     ▼
Terminal ileum colonization
     │  invasin → β1 integrin (M cells)
     ▼
Peyer's patch invasion ── (gut proteases degrade invasin: limiting)
     │  CD103+ DC / monocyte uptake
     ▼
Mesenteric lymph nodes ──► spleen/liver (dissemination)
     │  37°C → VirF/LcrF → T3SS
     ▼
Yop injection (YopH/E/T/O/P-J/M)
  inhibits phagocytosis, NF-κB/MAPK, inflammasome
     │
┌────────────┼───────────────────────────┐
▼            ▼                            ▼
  Enterocolitis /   Branch A: IRON OVERLOAD    Branch B: POST-INFECTION
  pseudoappendicitis  + deferoxamine            HLA-B27 → reactive arthritis
  (+ YstA enterotoxin) → SEPTICEMIA,            OmpF≈TSHR mimicry → Graves'
   → diarrhea        hepatic/splenic abscess    erythema nodosum, uveitis

Upstream vs downstream. Invasin-mediated M-cell entry is the upstream initiating event; T3SS/Yop immune subversion is the central amplifying node; enterocolitis, septicemia, and autoimmune sequelae are downstream outcomes gated by host iron status and HLA background.

Evidence Base (key literature)

PMID Contribution Type
26403101 Swine/pork as reservoir & main infection source Review
29307129 9.31% pig-tonsil prevalence; 4/O:3 = 95.74% Surveillance
12019084 Deferoxamine lowers LD₅₀ >5 log; deferiprone does not Model organism
31219970 Transfusional iron overload → fulminant yersiniosis Case report
27107739 Invasin-dependent DC/M-cell uptake & dissemination Mechanistic
22563435 YopJ inhibits survival pathways → macrophage death Mechanistic
40473988 Y. enterocolitica as post-enteric ReA trigger Review
7221767 ReA linked to HLA-B27 Case report
32564766 Graves' association OR 6.12 (3.71–10.10) Meta-analysis
20484489 OmpF–TSHR molecular mimicry In vitro
42720049 Rising US incidence; pork 46%, dairy 18% Surveillance
19219471 Culture/cold-enrichment diagnostics; bioserotype prevalence Surveillance
10803262 3rd-gen cephalosporins & ciprofloxacin most active In vitro
1952849 Fluoroquinolone efficacy vs β-lactam failure Model organism
15254824 Three clinical syndromes defined Review
19058737 Slaughter hygiene as key prevention Surveillance
8363822 Rodent model fidelity to human disease Review
28400007 ystA best pathogenicity marker; ystB for 1A Molecular
28283072 ail as main chromosomal virulence marker Molecular
41539755 Psychrotolerance/biofilm across cold chain Surveillance

Limitations and Knowledge Gaps

  • No human genetic causal architecture — as an infectious disease, sections on causal genes, pathogenic ACMG variants, inheritance, penetrance, and carrier frequency are not applicable; only host modifiers (HLA-B27, iron-handling) are relevant.
  • Quantitative human epidemiology is incomplete here — precise population incidence/prevalence per 100,000 and absolute mortality rates were not extracted; the strongest quantitative signal is the documented US incidence increase rather than an absolute rate.
  • Causal certainty of autoimmune sequelae — the Graves'/AITD association is epidemiological (OR-based meta-analysis) plus a plausible mimicry mechanism; direct causation in humans remains inferential.
  • Model–strain mismatch — much mechanistic work uses highly pathogenic 1B/O:8 mouse strains, whereas most human disease is 4/O:3; findings may not fully transfer.
  • Effect sizes for some clinical claims (e.g., proportion progressing to septicemia, ReA incidence specifically after Yersinia) rely on case series and reviews rather than large cohorts.

Proposed Follow-up Actions

  1. Extract absolute incidence/prevalence from GBD, CDC FoodNet, and Orphanet to complete Section 9 quantitatively.
  2. Systematic review of HLA-B27 penetrance for Yersinia-triggered reactive arthritis (attributable risk, time-to-onset).
  3. Prospective study of oral iron-chelator choice (deferiprone/deferasirox vs deferoxamine) on yersiniosis incidence in transfusion-dependent patients.
  4. Genomic surveillance (One Health) linking swine and human isolates via SNP/MLST to quantify attributable transmission and AMR gene flow (PMID: 41413462).
  5. 4/O:3-based infection models to align mechanistic studies with the globally dominant human bioserotype.
  6. Mechanistic test of OmpF–TSHR mimicry in vivo to establish causality for the Graves' association.

Report compiled from 13 confirmed findings across 73 reviewed papers over 5 investigation iterations. Evidence types are labeled (human clinical, model organism, in vitro, computational, surveillance/review) throughout.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

Outcome Count
References checked 54
Resolved 54
Unresolved (possible confabulation) 0
Unverifiable 0
Quoted claims checked 2
Quoted claims found in source 1
Quoted claims not found in source 1
References weighed for topical relevance 54
On topic 19
Off topic 0

Quotes not found in the cited source

Searched the abstract, any retrieved full text, and the title. A quote drawn from a part of the paper that was not retrieved will appear here too, so check before treating one as invented:

Every one of these was searched against an abstract alone, with no full text retrieved - marked abstract only below. Where full text can be fetched, re-running with it will settle them; where the source publishes only a summary to PubMed, as GeneReviews chapters do, it will not, and the quote has to be checked by hand against the chapter itself.

  • PMID:19058737 (abstract only): "Good hygienic slaughter practices are essential to prevent contamination of pork"
  • closest text in source: "Good hygienic slaughter practices are essential to prevent the contamination of pork with pathogenic Y"

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 35
Resolved 34
Unresolved (possible confabulation) 0
Obsolete 1
Unverifiable 0
Terms whose name was checked 18
Terms named correctly 3
Terms named as a different term 11
Terms whose name is worth a second look 4

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • HP:0002014 (1 mention) - the report calls it "Very common in enterocolitis"; HP calls it Diarrhea
  • HP:0001945 (1 mention) - the report calls it "Common"; HP calls it Fever
  • HP:0002605 (1 mention) - the report calls it "approximate"; HP calls it Hepatic necrosis
  • HP:0100806 (1 mention) - the report calls it "Rare; iron-overloaded/immunocompromised"; HP calls it Sepsis
  • HP:0001369 (1 mention) - the report calls it "~1/1000 (ReA overall); young adults 18–40"; HP calls it Arthritis
  • HP:0012219 (1 mention) - the report calls it "Occasional"; HP calls it Erythema nodosum
  • HP:0000554 (1 mention) - the report calls it "Occasional"; HP calls it Uveitis
  • HP:0100647 (1 mention) - the report calls it "Association (see §5)"; HP calls it Graves disease
  • GO:0030260 (1 mention) - the report calls it "entry into host cell"; GO calls it GO_0030260
  • CHEBI:18248 (1 mention) - the report calls it "CHEBI entities: iron"; CHEBI calls it iron atom**
  • UBERON:0002107 (1 mention) - the report calls it "liver", "Secondary organ involvement: liver"; UBERON calls it liver

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

  • GO:0030260 (GO_0030260) (1 mention) - replaced by GO:0044409

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • HP:0002583 (1 mention) - the report calls it "enterocolitis"; HP calls it Colitis
  • GO:0052031 (1 mention) - the report calls it "modulation by symbiont of host defense response"; GO calls it symbiont-mediated perturbation of host defense response, and lists "modulation by symbiont of host defense response" among its other names
  • GO:0043123 (1 mention) - the report calls it "positive regulation of NF-κB signaling — inhibited"; GO calls it positive regulation of canonical NF-kappaB signal transduction, and lists "positive regulation of I-kappaB kinase/NF-kappaB signaling" among its other names
  • UBERON:0001211 (1 mention) - the report calls it "Peyer's patches"; UBERON calls it Peyer's patch

Terms named inconsistently

The report gives these identifiers more than one name of its own:

  • UBERON:0002107 - called "liver", "Secondary organ involvement: liver"