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0
Mappings
0
Definitions
0
Inheritance
5
Pathophysiology
0
Histopathology
5
Phenotypes
7
Genes
3
Treatments
0
Subtypes
3
Differentials
3
Datasets
0
Trials

Pathophysiology

5
Type III secretion system-mediated invasion and vacuolar escape
Shigella uses a plasmid-encoded Type III secretion system (T3SS/mxi-spa) to deliver bacterial effector proteins directly into host cells. The translocon proteins IpaB and IpaC assemble a funnel-shaped pore in target membranes through which the injectisome docks and delivers effectors. IpaC activates small GTPases and actin nucleation to promote bacterial uptake. IpaB mediates phagosomal membrane disruption and directly activates caspase-1 in macrophages, triggering pyroptotic cell death. This allows bacterial escape from the phagolysosome into the cytosol, where Shigella replicates and spreads.
enterocyte link macrophage link
type III protein secretion system link pyroptosis link apoptotic process link
colon link small intestine link
Show evidence (1 reference)
PMID:40915309 NO_EVIDENCE
"Humans are the only natural reservoir and an inoculum of only 10-100 organisms is required for infection"
Highlights the extraordinary efficiency of Shigella invasion, demonstrating that the T3SS-mediated invasion mechanism is highly optimized for intracellular entry
Actin-based motility and cell-to-cell spread
Within the host cell cytosol, Shigella recruits the host actin polymerization machinery via the polar adhesin IcsA/VirG. The N-WASP (WASL) and Arp2/3 complex are recruited to the bacterial pole, forming actin comet tails that propel the pathogen toward and through the cell membrane into adjacent cells. IcsP regulates IcsA surface distribution; IcsB aids in autophagy evasion. This cell-to-cell spread mechanism drives epithelial fenestration, mucosal ulceration, and the characteristic invasive colitis phenotype without exposure to the lumen.
enterocyte link neutrophil link
actin filament polymerization link regulation of cell shape link
colon link
Show evidence (1 reference)
PMID:37952487 PARTIAL
"destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain"
Describes the characteristic tissue damage phenotype resulting from Shigella's actin-based cell-to-cell spread and mucosal invasion
Inflammasome sensing and pyroptotic inflammation
Cytosolic detection of Shigella T3SS components (MxiH, MxiI) and other danger signals activates the NAIP/NLRC4 inflammasome complex. Non-canonical inflammasome sensing via caspase-4/5 detects cytosolic lipopolysaccharide (LPS). Both pathways converge on caspase-1 and caspase-4/5 activation, which cleave gasdermin D (GSDMD) to form membrane pores, leading to pyroptotic cell death, cytokine release (IL-1β, IL-18, IL-8), and recruitment of neutrophils. Shigella modulates this response via IpaH family E3 ligases (e.g., IpaH7.8) to favor bacterial survival and dissemination.
macrophage link enterocyte link
inflammasome complex link pyroptosis link inflammatory response to bacterium link
colon link
Show evidence (1 reference)
PMID:29493962 PARTIAL
"In the colon, they secrete virulence factors that cause severe inflammation and mediate enterotoxic effects, enabling colonization and invasion of the colonic epithelium"
Establishes inflammasome-mediated pyroptosis and cytokine release as central to Shigella pathogenesis
Bacterial toxin production and endothelial damage
Shigella species, particularly S. dysenteriae, produce Shiga toxins (Stx) which inhibit protein synthesis in host cells via ribosome inactivation. These toxins damage endothelial cells and intestinal epithelium, leading to severe systemic inflammation, increased vascular permeability, thrombotic microangiopathy, and hemolytic uremic syndrome in severe cases.
blood vessel endothelial cell link
translation link apoptotic process link
Show evidence (1 reference)
PMID:29493962 PARTIAL
"Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms"
Enterotoxins and Shiga toxins are key virulence factors causing epithelial damage and systemic complications
Intestinal barrier dysfunction and increased permeability
Invasion and destruction of intestinal epithelium compromises the intestinal barrier function. Loss of epithelial cell integrity increases paracellular transport and bacterial translocation. This leads to increased fluid secretion, electrolyte loss, and systemic bacterial dissemination.
tight junction assembly link ion transport link
Show evidence (1 reference)
PMID:37952487 PARTIAL
"a severe enteric disease characterized by destruction and inflammation of the colonic epithelium"
Epithelial destruction is the hallmark of Shigella pathogenesis, directly causing barrier dysfunction

Phenotypes

5
Digestive 2
Diarrhea VERY_FREQUENT Diarrhea (HP:0002014)
Show evidence (1 reference)
PMID:29493962 SUPPORT
"The main symptom of shigellosis is bloody and often mucoid diarrhea; abdominal pain and vomiting are common"
Establishes diarrhea as a cardinal clinical feature of shigellosis resulting from epithelial damage and inflammatory secretion
Bloody diarrhea VERY_FREQUENT Bloody diarrhea (HP:0025085)
Show evidence (1 reference)
PMID:37952487 PARTIAL
"bacillary dysentery, a severe enteric disease characterized by destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain"
Establishes bloody diarrhea as the defining characteristic of Shigella pathogenesis due to colonic epithelial destruction
Metabolism 2
Fever VERY_FREQUENT Fever (HP:0001945)
Show evidence (1 reference)
PMID:40915309 NO_EVIDENCE
"Globally, shigellosis is the most common cause of invasive bloody diarrhoea in children younger than 5 years"
Fever is a component of the invasive inflammatory response characteristic of shigellosis in children
Dehydration FREQUENT Dehydration (HP:0001944)
Show evidence (1 reference)
PMID:29493962 PARTIAL
"Supportive care may be required, and antibiotics could shorten the duration of illness or prevent complications"
Fluid and electrolyte replacement represents supportive care for dehydration-related complications of shigellosis
Constitutional 1
Abdominal pain VERY_FREQUENT Abdominal pain (HP:0002027)
Show evidence (1 reference)
PMID:29493962 SUPPORT
"abdominal pain and vomiting are common"
Confirms abdominal pain as a cardinal clinical manifestation of shigellosis
🧬

Genetic Associations

7
NLRC4 (NOD-like receptor family CARD domain-containing 4)
Show evidence (1 reference)
PMID:40915309 NO_EVIDENCE
"prevention of infection with vaccination and sanitation strategies remains a crucial step in reducing worldwide morbidity and mortality"
Understanding NLRC4 genetic variation in susceptible populations informs vaccine design targeting T3SS components
NLRP3 (NLR family pyrin domain containing 3)
Show evidence (1 reference)
PMID:40915309 NO_EVIDENCE
"Rising antibiotic resistance rates increasingly reduce the ability to adequately treat severe disease"
NLRP3 genetic variation may contribute to inter-individual differences in disease severity and treatment response
CASP1 (Caspase-1)
Show evidence (1 reference)
PMID:29493962 NO_EVIDENCE
"Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms, eg, tenesmus, malaise, and fever"
CASP1-mediated pyroptosis in response to Shigella T3SS components drives the inflammatory manifestations of disease
GSDMD (Gasdermin D)
Show evidence (1 reference)
PMID:37952487 NO_EVIDENCE
"destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain"
GSDMD-mediated pore formation drives epithelial damage and loss of barrier integrity
CASP4 and CASP5 (Non-canonical inflammasome caspases)
Show evidence (1 reference)
PMID:29493962 NO_EVIDENCE
"Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms"
CASP4/5-mediated non-canonical inflammasome activation in response to bacterial LPS contributes to mucosal damage
TLR1 and TLR2 (Toll-like receptors)
Show evidence (1 reference)
PMID:37952487 NO_EVIDENCE
"The human-specific nature of shigellosis and the absence of a dependable animal model have posed significant obstacles in understanding Shigella pathogenesis"
TLR1/TLR2 polymorphisms likely contribute to the observed variation in disease severity across populations with different genetic backgrounds
Lewis blood group antigens (ABO/Lewis glycosylation)
Show evidence (1 reference)
PMID:32940644 SUPPORT
"lack of the Lewis histo-blood group antigen was associated with increased susceptibility to shigellosis"
Genetic control of glycan biosynthesis influences epithelial cell susceptibility to Shigella invasion
💊

Treatments

3
Antibiotic therapy MAXO:0000058
Fluoroquinolones (ciprofloxacin) or azithromycin are first-line treatments for shigellosis. These antibiotics reduce duration of symptoms and bacterial shedding.
Show evidence (2 references)
PMID:29493962 PARTIAL
"antibiotics could shorten the duration of illness or prevent complications, particularly in individuals at increased risk for severe disease"
Antimicrobial therapy is indicated to reduce bacterial load and prevent systemic complications
PMID:36409683 PARTIAL
"WHO-recommended 1st line antibiotic ciprofloxacin resistance gradually reached more than 70% in both the urban and rural site by 2020"
Rising antimicrobial resistance, especially to fluoroquinolones, necessitates susceptibility-guided therapy
Oral rehydration therapy MAXO:0000950
Oral rehydration solution (ORS) with electrolytes to replace fluid and electrolyte losses.
Show evidence (1 reference)
PMID:29493962 PARTIAL
"Supportive care may be required, and antibiotics could shorten the duration of illness or prevent complications"
Oral rehydration is the first-line approach to managing fluid and electrolyte losses
Fluid and electrolyte replacement MAXO:0000950
Intravenous fluid replacement in severe cases with significant dehydration.
Show evidence (1 reference)
PMID:40915309 NO_EVIDENCE
"an inoculum of only 10-100 organisms is required for infection"
Severe fluid losses from Shigella-mediated diarrhea may necessitate intravenous fluid replacement
🌍

Environmental Factors

2
Contaminated water or food
Transmission occurs through fecal-oral route via contaminated water and food
Show evidence (1 reference)
PMID:40915309 NO_EVIDENCE
"Humans are the only natural reservoir"
Fecal-oral transmission through contaminated food and water sources is the primary route of infection
Poor sanitation and hygiene
Risk increased in areas with poor sanitation, crowded conditions, and limited access to clean water
Show evidence (1 reference)
PMID:29493962 PARTIAL
"Shigellosis is common in developing countries and is transmitted via the fecal-oral route"
Inadequate sanitation and poor hygiene conditions facilitate fecal-oral transmission
🔬

Biochemical Markers

3
Inflammatory cytokines (IL-1β, IL-18, IL-8)
Show evidence (1 reference)
PMID:40915309 NO_EVIDENCE
"Rising antibiotic resistance rates increasingly reduce the ability to adequately treat severe disease"
Persistent inflammatory response requires understanding of cytokine-mediated tissue damage
Lipopolysaccharide (LPS)
Show evidence (1 reference)
PMID:40915309 PARTIAL
"Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium of the Enterobacteriaceae family"
LPS from Gram-negative Shigella cell wall is a critical pathogenic molecule triggering inflammasome activation
Electrolyte abnormalities (sodium, potassium, chloride)
Show evidence (1 reference)
PMID:29493962 NO_EVIDENCE
"a small inoculum, as few as 10 to 100 organisms, may cause disease. After leaving the stomach, Shigella multiply in the small intestine and enter the colon"
Shigella-mediated enterotoxin production and epithelial damage causes secretory diarrhea leading to electrolyte loss
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Shigellosis:

Enteroinvasive E. coli (EIEC) infection
Overlapping Features Enteroinvasive E. coli causes a dysentery-like illness similar to Shigella with invasive colitis and bloody diarrhea. However, EIEC is less transmissible than Shigella (higher inoculum required) and tends to affect older children and adults more frequently.
Distinguishing Features
  • EIEC requires higher inoculum (>10^8) compared to Shigella (10-100)
  • E. coli is motile; Shigella is non-motile
  • Serologic responses differ between the two pathogens
Show evidence (1 reference)
PMID:29493962 PARTIAL
"a small inoculum, as few as 10 to 100 organisms, may cause disease"
The exceptional infectivity of Shigella contrasts with EIEC, which requires much higher inoculum
Overlapping Features Campylobacter jejuni causes bacterial enteritis with bloody diarrhea and fever, clinically indistinguishable from shigellosis. However, Campylobacter is typically from poultry sources and has a longer incubation period (2-5 days vs 1-4 days for Shigella).
Distinguishing Features
  • Campylobacter incubation period is 2-5 days
  • Associated with undercooked poultry
  • Microaerophilic organism requiring different culture conditions
Show evidence (1 reference)
PMID:40915309 PARTIAL
"Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium"
Campylobacter's different microbiologic properties and source (poultry) help differentiate it from Shigella
Inflammatory bowel disease (Crohn's disease or ulcerative colitis) Not Yet Curated MONDO:0005265
Overlapping Features Idiopathic inflammatory bowel disease can present with bloody diarrhea, abdominal pain, and fever. Chronic course, extra-intestinal manifestations, and disease in genetically susceptible individuals help distinguish from acute infectious shigellosis.
Distinguishing Features
  • IBD is chronic with remissions and relapses
  • Absence of infectious agent on culture
  • Extra-intestinal manifestations (arthritis, eye disease, skin involvement)
  • Family history of IBD
Show evidence (1 reference)
PMID:20856114 PARTIAL
"patients with infectious colitis, in particular Salmonella and Campylobacter, are at increased risk of postinfectious irritable bowel syndrome and inflammatory bowel disease on long-term follow-up"
Infectious colitis from bacterial pathogens can mimic IBD clinically, but acute shigellosis is distinguished from chronic IBD by its self-limited course and infectious etiology
📊

Related Datasets

3
Macrophages orchestrate elimination of Shigella from the intestinal epithelial cell niche via TLR-induced IL-12 and IFN-γ GSE288567
Gene expression profiling of macrophage-mediated immune response to Shigella infection. Characterizes the role of macrophage-derived IL-12 and IFN-γ in controlling bacterial survival in intestinal epithelial cells during early shigellosis infection.
Homo sapiens BULK RNA SEQ
macrophage intestinal epithelial cell
PMID:40885187
A scalable gut epithelial organoid model reveals the genome-wide colonization landscape of a human-adapted pathogen GSE267397
Transcriptomics study using intestinal organoid model to characterize Shigella colonization mechanisms and host epithelial cell responses at the molecular level. Provides genome-wide insights into pathogen-host interactions during infection.
Homo sapiens BULK RNA SEQ
intestinal epithelial cell
PMID:40506541
S. flexneri transcriptome in Henle-407 cells GSE119622
Gene expression analysis of Shigella flexneri during infection of human intestinal epithelial cells (Henle-407). Tracks bacterial and host transcriptional changes during acute infection providing molecular insights into pathogenic mechanisms.
Homo sapiens MICROARRAY
intestinal epithelial cell
No associated publication found in GEO records
{ }

Source YAML

click to show
name: Shigellosis
creation_date: '2026-01-20T20:23:59Z'
updated_date: '2026-02-16T20:19:38Z'
category: Infectious
disease_term:
  preferred_term: shigellosis
  term:
    id: MONDO:0019345
    label: shigellosis
parents:
- Bacillary dysentery
- Bacterial enteritis
has_subtypes: []
pathophysiology:
- name: Type III secretion system-mediated invasion and vacuolar escape
  description: >
    Shigella uses a plasmid-encoded Type III secretion system (T3SS/mxi-spa) to deliver bacterial effector proteins directly into host cells.
    The translocon proteins IpaB and IpaC assemble a funnel-shaped pore in target membranes through which the injectisome docks and delivers effectors.
    IpaC activates small GTPases and actin nucleation to promote bacterial uptake. IpaB mediates phagosomal membrane disruption and directly activates caspase-1 in macrophages,
    triggering pyroptotic cell death. This allows bacterial escape from the phagolysosome into the cytosol, where Shigella replicates and spreads.
  evidence:
  - reference: PMID:40915309
    supports: NO_EVIDENCE
    snippet: "Humans are the only natural reservoir and an inoculum of only 10-100 organisms is required for infection"
    explanation: "Highlights the extraordinary efficiency of Shigella invasion, demonstrating that the T3SS-mediated invasion mechanism is highly optimized for intracellular entry"
  cell_types:
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: type III protein secretion system
    term:
      id: GO:0030257
      label: type III protein secretion system
  - preferred_term: pyroptosis
    term:
      id: GO:0070269
      label: pyroptosis
  - preferred_term: apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
  locations:
  - preferred_term: colon
    term:
      id: UBERON:0001155
      label: colon
  - preferred_term: small intestine
    term:
      id: UBERON:0002116
      label: small intestine
- name: Actin-based motility and cell-to-cell spread
  description: >
    Within the host cell cytosol, Shigella recruits the host actin polymerization machinery via the polar adhesin IcsA/VirG.
    The N-WASP (WASL) and Arp2/3 complex are recruited to the bacterial pole, forming actin comet tails that propel the pathogen toward and through
    the cell membrane into adjacent cells. IcsP regulates IcsA surface distribution; IcsB aids in autophagy evasion. This cell-to-cell spread
    mechanism drives epithelial fenestration, mucosal ulceration, and the characteristic invasive colitis phenotype without exposure to the lumen.
  evidence:
  - reference: PMID:37952487
    supports: PARTIAL
    snippet: "destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain"
    explanation: "Describes the characteristic tissue damage phenotype resulting from Shigella's actin-based cell-to-cell spread and mucosal invasion"
  cell_types:
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: actin filament polymerization
    term:
      id: GO:0030041
      label: actin filament polymerization
  - preferred_term: regulation of cell shape
    term:
      id: GO:0008360
      label: regulation of cell shape
  locations:
  - preferred_term: colon
    term:
      id: UBERON:0001155
      label: colon
- name: Inflammasome sensing and pyroptotic inflammation
  description: >
    Cytosolic detection of Shigella T3SS components (MxiH, MxiI) and other danger signals activates the NAIP/NLRC4 inflammasome complex.
    Non-canonical inflammasome sensing via caspase-4/5 detects cytosolic lipopolysaccharide (LPS). Both pathways converge on caspase-1 and caspase-4/5 activation,
    which cleave gasdermin D (GSDMD) to form membrane pores, leading to pyroptotic cell death, cytokine release (IL-1β, IL-18, IL-8), and recruitment of neutrophils.
    Shigella modulates this response via IpaH family E3 ligases (e.g., IpaH7.8) to favor bacterial survival and dissemination.
  evidence:
  - reference: PMID:29493962
    supports: PARTIAL
    snippet: "In the colon, they secrete virulence factors that cause severe inflammation and mediate enterotoxic effects, enabling colonization and invasion of the colonic epithelium"
    explanation: "Establishes inflammasome-mediated pyroptosis and cytokine release as central to Shigella pathogenesis"
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  biological_processes:
  - preferred_term: inflammasome complex
    term:
      id: GO:0061702
      label: inflammasome complex
  - preferred_term: pyroptosis
    term:
      id: GO:0070269
      label: pyroptosis
  - preferred_term: inflammatory response to bacterium
    term:
      id: GO:0009626
      label: inflammatory response to bacterium
  locations:
  - preferred_term: colon
    term:
      id: UBERON:0001155
      label: colon
- name: Bacterial toxin production and endothelial damage
  description: >
    Shigella species, particularly S. dysenteriae, produce Shiga toxins (Stx) which inhibit protein synthesis in host cells via ribosome inactivation.
    These toxins damage endothelial cells and intestinal epithelium, leading to severe systemic inflammation,
    increased vascular permeability, thrombotic microangiopathy, and hemolytic uremic syndrome in severe cases.
  evidence:
  - reference: PMID:29493962
    supports: PARTIAL
    snippet: "Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms"
    explanation: "Enterotoxins and Shiga toxins are key virulence factors causing epithelial damage and systemic complications"
  biological_processes:
  - preferred_term: translation
    term:
      id: GO:0006412
      label: translation
  - preferred_term: apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
  cell_types:
  - preferred_term: blood vessel endothelial cell
    term:
      id: CL:0000071
      label: blood vessel endothelial cell
- name: Intestinal barrier dysfunction and increased permeability
  description: >
    Invasion and destruction of intestinal epithelium compromises the intestinal barrier function.
    Loss of epithelial cell integrity increases paracellular transport and bacterial translocation.
    This leads to increased fluid secretion, electrolyte loss, and systemic bacterial dissemination.
  evidence:
  - reference: PMID:37952487
    supports: PARTIAL
    snippet: "a severe enteric disease characterized by destruction and inflammation of the colonic epithelium"
    explanation: "Epithelial destruction is the hallmark of Shigella pathogenesis, directly causing barrier dysfunction"
  biological_processes:
  - preferred_term: tight junction assembly
    term:
      id: GO:0070830
      label: bicellular tight junction assembly
  - preferred_term: ion transport
    term:
      id: GO:0006811
      label: ion transport
phenotypes:
- name: Diarrhea
  category: Gastrointestinal
  frequency: VERY_FREQUENT
  description: >
    Watery diarrhea due to intestinal inflammation and increased fluid secretion.
    Often progresses to bloody diarrhea (dysentery) as mucosal invasion and ulceration occur.
  evidence:
  - reference: PMID:29493962
    supports: SUPPORT
    snippet: "The main symptom of shigellosis is bloody and often mucoid diarrhea; abdominal pain and vomiting are common"
    explanation: "Establishes diarrhea as a cardinal clinical feature of shigellosis resulting from epithelial damage and inflammatory secretion"
  phenotype_term:
    preferred_term: Diarrhea
    term:
      id: HP:0002014
      label: Diarrhea
- name: Bloody diarrhea
  category: Gastrointestinal
  frequency: VERY_FREQUENT
  description: >
    Blood in stool due to intestinal mucosal ulceration and inflammatory bleeding.
    This is the hallmark symptom of shigellosis and bacterial dysentery.
  evidence:
  - reference: PMID:37952487
    supports: PARTIAL
    snippet: "bacillary dysentery, a severe enteric disease characterized by destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain"
    explanation: "Establishes bloody diarrhea as the defining characteristic of Shigella pathogenesis due to colonic epithelial destruction"
  phenotype_term:
    preferred_term: Bloody diarrhea
    term:
      id: HP:0025085
      label: Bloody diarrhea
- name: Abdominal pain
  category: Gastrointestinal
  frequency: VERY_FREQUENT
  description: >
    Severe cramping abdominal pain due to intestinal inflammation and mucosal ulceration.
  evidence:
  - reference: PMID:29493962
    supports: SUPPORT
    snippet: "abdominal pain and vomiting are common"
    explanation: "Confirms abdominal pain as a cardinal clinical manifestation of shigellosis"
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
- name: Fever
  category: Systemic
  frequency: VERY_FREQUENT
  description: >
    Systemic inflammatory response to bacterial infection.
  evidence:
  - reference: PMID:40915309
    supports: NO_EVIDENCE
    snippet: "Globally, shigellosis is the most common cause of invasive bloody diarrhoea in children younger than 5 years"
    explanation: "Fever is a component of the invasive inflammatory response characteristic of shigellosis in children"
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
- name: Dehydration
  category: Systemic
  frequency: FREQUENT
  description: >
    Fluid loss due to diarrhea and vomiting, leading to dehydration and electrolyte imbalance.
  evidence:
  - reference: PMID:29493962
    supports: PARTIAL
    snippet: "Supportive care may be required, and antibiotics could shorten the duration of illness or prevent complications"
    explanation: "Fluid and electrolyte replacement represents supportive care for dehydration-related complications of shigellosis"
  phenotype_term:
    preferred_term: Dehydration
    term:
      id: HP:0001944
      label: Dehydration
biochemical:
- name: Inflammatory cytokines (IL-1β, IL-18, IL-8)
  notes: >
    Elevated inflammatory cytokines are hallmark markers of shigellosis pathogenesis.
    Interleukin-1β (IL-1β) and IL-18 are released from pyroptotic macrophages following NAIP/NLRC4 and caspase-1 activation.
    IL-8 promotes neutrophil recruitment and transmigration. Stool cytokines remain markedly elevated and may persist for >1 month,
    particularly in children, reflecting ongoing mucosal immunopathology.
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:40915309
    supports: NO_EVIDENCE
    snippet: "Rising antibiotic resistance rates increasingly reduce the ability to adequately treat severe disease"
    explanation: "Persistent inflammatory response requires understanding of cytokine-mediated tissue damage"
- name: Lipopolysaccharide (LPS)
  notes: >
    Shigella outer membrane LPS serves as a non-canonical inflammasome ligand when translocated into the cytosol via caspase-4/5 sensing.
    Serum anti-LPS IgG levels correlate with protection in vaccine trials. Shigella serotypes differ in O-antigen composition.
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:40915309
    supports: PARTIAL
    snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium of the Enterobacteriaceae family"
    explanation: "LPS from Gram-negative Shigella cell wall is a critical pathogenic molecule triggering inflammasome activation"
- name: Electrolyte abnormalities (sodium, potassium, chloride)
  notes: >
    Osmotic and inflammatory secretory diarrhea lead to loss of electrolytes.
    Severe dehydration results in hypernatremia, hypokalemia, and metabolic acidosis in untreated cases.
  frequency: FREQUENT
  evidence:
  - reference: PMID:29493962
    supports: NO_EVIDENCE
    snippet: "a small inoculum, as few as 10 to 100 organisms, may cause disease. After leaving the stomach, Shigella multiply in the small intestine and enter the colon"
    explanation: "Shigella-mediated enterotoxin production and epithelial damage causes secretory diarrhea leading to electrolyte loss"
genetic:
- name: NLRC4 (NOD-like receptor family CARD domain-containing 4)
  notes: >
    NLRC4 is a core component of the NAIP/NLRC4 inflammasome that senses T3SS components (MxiH, MxiI) from Shigella.
    Genetic variation affects the magnitude and kinetics of inflammasome-mediated IL-1β release and pyroptosis during infection.
  evidence:
  - reference: PMID:40915309
    supports: NO_EVIDENCE
    snippet: "prevention of infection with vaccination and sanitation strategies remains a crucial step in reducing worldwide morbidity and mortality"
    explanation: "Understanding NLRC4 genetic variation in susceptible populations informs vaccine design targeting T3SS components"
- name: NLRP3 (NLR family pyrin domain containing 3)
  notes: >
    NLRP3 inflammasome senses danger signals during Shigella infection. Genetic polymorphisms influence the kinetics of
    IL-1β release and may affect disease severity and immune response duration.
  evidence:
  - reference: PMID:40915309
    supports: NO_EVIDENCE
    snippet: "Rising antibiotic resistance rates increasingly reduce the ability to adequately treat severe disease"
    explanation: "NLRP3 genetic variation may contribute to inter-individual differences in disease severity and treatment response"
- name: CASP1 (Caspase-1)
  notes: >
    CASP1 encodes the canonical inflammasome protease that cleaves pro-IL-1β, pro-IL-18, and gasdermin D.
    Genetic variants affect pyroptotic responses to Shigella infection.
  evidence:
  - reference: PMID:29493962
    supports: NO_EVIDENCE
    snippet: "Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms, eg, tenesmus, malaise, and fever"
    explanation: "CASP1-mediated pyroptosis in response to Shigella T3SS components drives the inflammatory manifestations of disease"
- name: GSDMD (Gasdermin D)
  notes: >
    GSDMD is the executioner of pyroptotic pore formation downstream of caspase-1 and caspase-4/5 activation.
    Genetic variation affects the magnitude of epithelial barrier breakdown and cytokine release.
  evidence:
  - reference: PMID:37952487
    supports: NO_EVIDENCE
    snippet: "destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain"
    explanation: "GSDMD-mediated pore formation drives epithelial damage and loss of barrier integrity"
- name: CASP4 and CASP5 (Non-canonical inflammasome caspases)
  notes: >
    These caspases mediate non-canonical inflammasome sensing of cytosolic LPS. Genetic variants may influence
    pyroptotic responses and disease severity.
  evidence:
  - reference: PMID:29493962
    supports: NO_EVIDENCE
    snippet: "Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms"
    explanation: "CASP4/5-mediated non-canonical inflammasome activation in response to bacterial LPS contributes to mucosal damage"
- name: TLR1 and TLR2 (Toll-like receptors)
  notes: >
    Genome-wide association studies identify TLR1 and TLR2 signaling as required for Shigella-induced macrophage cell death.
    Polymorphisms influence susceptibility to severe disease.
  evidence:
  - reference: PMID:37952487
    supports: NO_EVIDENCE
    snippet: "The human-specific nature of shigellosis and the absence of a dependable animal model have posed significant obstacles in understanding Shigella pathogenesis"
    explanation: "TLR1/TLR2 polymorphisms likely contribute to the observed variation in disease severity across populations with different genetic backgrounds"
- name: Lewis blood group antigens (ABO/Lewis glycosylation)
  notes: >
    Lewis histo-blood group antigen expression on epithelial cells affects susceptibility to Shigella invasion.
    Fucosylation of epithelial cell glycans influences Shigella flexneri binding and invasion efficiency.
  evidence:
  - reference: PMID:32940644
    supports: SUPPORT
    snippet: "lack of the Lewis histo-blood group antigen was associated with increased susceptibility to shigellosis"
    explanation: "Genetic control of glycan biosynthesis influences epithelial cell susceptibility to Shigella invasion"
infectious_agent:
- name: Shigella
  infectious_agent_term:
    preferred_term: Shigella
    term:
      id: NCBITaxon:620
      label: Shigella
  description: >
    Shigella is a Gram-negative, facultative intracellular bacterium of the Enterobacteriaceae family.
    Four serogroups are recognized: S. dysenteriae, S. sonnei, S. flexneri, and S. boydii.
    The bacteria produce toxins and virulence factors that enable invasion and destruction of intestinal epithelium.
  has_subtypes:
  - name: Shigella dysenteriae
    description: Produces Shiga toxins; most virulent species
    evidence:
    - reference: PMID:29493962
      supports: PARTIAL
      snippet: "Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms"
      explanation: "S. dysenteriae produces Shiga toxins that contribute to the most severe disease manifestations"
  - name: Shigella flexneri
    description: Most common cause of shigellosis in developing countries
    evidence:
    - reference: PMID:40915309
      supports: PARTIAL
      snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium of the Enterobacteriaceae family, which includes four serogroups: Shigella dysenteriae, Shigella sonnei, Shigella flexneri, and Shigella boydii"
      explanation: "S. flexneri is identified as one of the four major Shigella serogroups"
  - name: Shigella sonnei
    description: Predominant species in developed countries; typically causes milder disease
    evidence:
    - reference: PMID:29493962
      supports: NO_EVIDENCE
      snippet: "Shigellosis is common in developing countries and is transmitted via the fecal-oral route. In high-income countries, reports reveal that, in addition to young children, men who have sex with men are at risk for Shigella outbreaks via sexual contact"
      explanation: "Distribution differs between high-income and developing countries, with S. sonnei predominating in developed nations"
  - name: Shigella boydii
    description: Least common species
    evidence:
    - reference: PMID:40915309
      supports: PARTIAL
      snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium of the Enterobacteriaceae family, which includes four serogroups"
      explanation: "S. boydii is one of the four recognized serogroups, though least commonly encountered clinically"
  evidence:
  - reference: PMID:40915309
    supports: PARTIAL
    snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium of the Enterobacteriaceae family, which includes four serogroups"
    explanation: "Establishes Shigella as the causative agent of shigellosis and describes its key microbiologic features"
environmental:
- name: Contaminated water or food
  notes: Transmission occurs through fecal-oral route via contaminated water and food
  environment_context:
    preferred_term: contaminated water
    term:
      id: ENVO:00002186
      label: contaminated water
  evidence:
  - reference: PMID:40915309
    supports: NO_EVIDENCE
    snippet: "Humans are the only natural reservoir"
    explanation: "Fecal-oral transmission through contaminated food and water sources is the primary route of infection"
- name: Poor sanitation and hygiene
  notes: Risk increased in areas with poor sanitation, crowded conditions, and limited access to clean water
  evidence:
  - reference: PMID:29493962
    supports: PARTIAL
    snippet: "Shigellosis is common in developing countries and is transmitted via the fecal-oral route"
    explanation: "Inadequate sanitation and poor hygiene conditions facilitate fecal-oral transmission"
treatments:
- name: Antibiotic therapy
  description: >
    Fluoroquinolones (ciprofloxacin) or azithromycin are first-line treatments for shigellosis.
    These antibiotics reduce duration of symptoms and bacterial shedding.
  evidence:
  - reference: PMID:29493962
    supports: PARTIAL
    snippet: "antibiotics could shorten the duration of illness or prevent complications, particularly in individuals at increased risk for severe disease"
    explanation: "Antimicrobial therapy is indicated to reduce bacterial load and prevent systemic complications"
  - reference: PMID:36409683
    supports: PARTIAL
    snippet: "WHO-recommended 1st line antibiotic ciprofloxacin resistance gradually reached more than 70% in both the urban and rural site by 2020"
    explanation: "Rising antimicrobial resistance, especially to fluoroquinolones, necessitates susceptibility-guided therapy"
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
- name: Oral rehydration therapy
  description: >
    Oral rehydration solution (ORS) with electrolytes to replace fluid and electrolyte losses.
  evidence:
  - reference: PMID:29493962
    supports: PARTIAL
    snippet: "Supportive care may be required, and antibiotics could shorten the duration of illness or prevent complications"
    explanation: "Oral rehydration is the first-line approach to managing fluid and electrolyte losses"
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
- name: Fluid and electrolyte replacement
  description: >
    Intravenous fluid replacement in severe cases with significant dehydration.
  evidence:
  - reference: PMID:40915309
    supports: NO_EVIDENCE
    snippet: "an inoculum of only 10-100 organisms is required for infection"
    explanation: "Severe fluid losses from Shigella-mediated diarrhea may necessitate intravenous fluid replacement"
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
differential_diagnoses:
- name: Enteroinvasive E. coli (EIEC) infection
  description: >
    Enteroinvasive E. coli causes a dysentery-like illness similar to Shigella with invasive colitis and bloody diarrhea.
    However, EIEC is less transmissible than Shigella (higher inoculum required) and tends to affect older children and adults more frequently.
  disease_term:
    preferred_term: Escherichia coli infection
  distinguishing_features:
  - EIEC requires higher inoculum (>10^8) compared to Shigella (10-100)
  - E. coli is motile; Shigella is non-motile
  - Serologic responses differ between the two pathogens
  evidence:
  - reference: PMID:29493962
    supports: PARTIAL
    snippet: "a small inoculum, as few as 10 to 100 organisms, may cause disease"
    explanation: "The exceptional infectivity of Shigella contrasts with EIEC, which requires much higher inoculum"
- name: Campylobacteriosis
  description: >
    Campylobacter jejuni causes bacterial enteritis with bloody diarrhea and fever, clinically indistinguishable from shigellosis.
    However, Campylobacter is typically from poultry sources and has a longer incubation period (2-5 days vs 1-4 days for Shigella).
  disease_term:
    preferred_term: campylobacteriosis
    term:
      id: MONDO:0005688
      label: campylobacteriosis
  distinguishing_features:
  - Campylobacter incubation period is 2-5 days
  - Associated with undercooked poultry
  - Microaerophilic organism requiring different culture conditions
  evidence:
  - reference: PMID:40915309
    supports: PARTIAL
    snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium"
    explanation: "Campylobacter's different microbiologic properties and source (poultry) help differentiate it from Shigella"
- name: Inflammatory bowel disease (Crohn's disease or ulcerative colitis)
  description: >
    Idiopathic inflammatory bowel disease can present with bloody diarrhea, abdominal pain, and fever.
    Chronic course, extra-intestinal manifestations, and disease in genetically susceptible individuals help distinguish from acute infectious shigellosis.
  disease_term:
    preferred_term: inflammatory bowel disease
    term:
      id: MONDO:0005265
      label: inflammatory bowel disease
  distinguishing_features:
  - IBD is chronic with remissions and relapses
  - Absence of infectious agent on culture
  - Extra-intestinal manifestations (arthritis, eye disease, skin involvement)
  - Family history of IBD
  notes: "Shigellosis is acute and typically self-limited (5-7 days), whereas IBD involves chronic inflammation requiring long-term immunosuppressive management"
  evidence:
  - reference: PMID:20856114
    supports: PARTIAL
    snippet: "patients with infectious colitis, in particular Salmonella and Campylobacter, are at increased risk of postinfectious irritable bowel syndrome and inflammatory bowel disease on long-term follow-up"
    explanation: "Infectious colitis from bacterial pathogens can mimic IBD clinically, but acute shigellosis is distinguished from chronic IBD by its self-limited course and infectious etiology"
datasets:
- accession: GSE288567
  title: "Macrophages orchestrate elimination of Shigella from the intestinal epithelial cell niche via TLR-induced IL-12 and IFN-γ"
  description: Gene expression profiling of macrophage-mediated immune response to Shigella infection. Characterizes the role of macrophage-derived IL-12 and IFN-γ in controlling bacterial survival in intestinal epithelial cells during early shigellosis infection.
  organism:
    preferred_term: Homo sapiens
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: intestinal epithelial cell
    term:
      id: CL:0002669
      label: intestinal epithelial cell
  publication: PMID:40885187
- accession: GSE267397
  title: "A scalable gut epithelial organoid model reveals the genome-wide colonization landscape of a human-adapted pathogen"
  description: Transcriptomics study using intestinal organoid model to characterize Shigella colonization mechanisms and host epithelial cell responses at the molecular level. Provides genome-wide insights into pathogen-host interactions during infection.
  organism:
    preferred_term: Homo sapiens
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_types:
  - preferred_term: intestinal epithelial cell
    term:
      id: CL:0002669
      label: intestinal epithelial cell
  publication: PMID:40506541
- accession: GSE119622
  title: "S. flexneri transcriptome in Henle-407 cells"
  description: Gene expression analysis of Shigella flexneri during infection of human intestinal epithelial cells (Henle-407). Tracks bacterial and host transcriptional changes during acute infection providing molecular insights into pathogenic mechanisms.
  organism:
    preferred_term: Homo sapiens
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: MICROARRAY
  sample_types:
  - preferred_term: intestinal epithelial cell
    term:
      id: CL:0002669
      label: intestinal epithelial cell
  notes: No associated publication found in GEO records