Enteric Bactria - Specific Pathogens Flashcards
What is the clinical presentation and serotype of Vibrio cholerae infection? Is it invasive or not?
Incubation period 2-5 days, abrupt onset of diarrhea, abdominal cramps, some vomiting. No fever. Milder to severe watery diarrhea - up to 15-20 liters/day leads to severe dehydration, blood pressure drop and vascular collapse, death if untreated.
Serotype - Vibrio cholerae has many serotypes, although it is frequently caused by organisms of serogroup O1.
Vibrio - Non-invasive
What are the pathology and pathogenic factors of V cholerae and ETEC?
Protoype toxigenic diarrheas - - V. cholerae, Enterotoxigenic E. coli (ETEC)
Infectious dose HIGH - 10^8, may drop to 10^4 when stomach acid is neutralized
1 - Adheres and colonizes small intestine - requires pili or fimbriae with specific receptors
2 - Enterotoxin made - B subunit binds receptor on enterocytes, enzymatic A subunit enters cell
3 - CT or LT enzymatically activate adenylate cyclase
ST activates guanylate cyclase
4 - Increased cAMP /cGMP results in Cl- secretion; HCO3- and H20 follow
What are the processes and factors required for cholera pathogenicity?
Colonization of small bowel and toxin production are essential prerequisites to disease. Both require factors encoded by different LYSOGENIC PHAGES - cholera is now added to the list of diseases where BACTERIOPHAGE CONVERSION is important.
a) Adherence factor (TCP pilus, toxin co-regulated pilus), which is also the coat protein of a phage encoding cholera toxin (CTX).
b) Cholera toxin production - genes chromosomally encoded as part of genome of phage CTX; this phage uses the TCP pilus as its receptor.
What is the structure and function of cholera toxin?
Cholera toxin structure and function - prototype A-B type toxin - B subunit binds to cell surface receptors (ganglioside GM1) of enterocytes. A subunit then enters the cell cytoplasm, where it transfers ADP-ribose from NAD to a regulatory G protein. This then constitutively activates adenylate cyclase, leading to increased cAMP concentrations, which leads to increased Cl- secretion, decreased Na+ absorption, and net secretion of fluid into the gut lumen. Cholera toxin is CYTOTONIC (i.e., it does NOT kill the cell); an intoxicated enterocyte continues secretion until it is replaced naturally.
What is the mode of transmission and treatment of cholera?
Mode of transmission
a) fecal/oral - generally through ingestion of contaminated foods
b) environmental reservoir - V. cholerae can be found in aquatic environments
Treatment
a) Restore fluid and electrolyte loss - milder cases can be orally rehydrated with salt/sugar solutions - ORS - isotonic Na/K, Cl, citrate or bicarbonate buffer and glucose. If ORS is not tolerated, intravenous rehydration with Ringers lactate + KCl.
Antibiotics shorten course of infection, number and volume of stools, and number of Vibrios excreted in the stool, and may help reduce carrier state.
What are the symptoms and treatment of ETEC infection?
Leading cause of traveler’s diarrhea for adults (up to 70%), important in infants and young children’s diarrhea in developing countries.
Symptoms - watery diarrhea, no blood or pus, rarely have low-grade fever, abdominal cramps, and vomiting. Can be severe, cholera-like diarrhea, even in adults.
Treatment is usually supportive due to acute onset, and self-limiting nature. Replace fluids and salt. Antibiotics not usually recommended, even prophylactically. Bismuth subsalicylate (pepto-Bismol) is helpful to relieve symptoms/shorten duration.
What is the pathogenesis of ETEC and what function in required for it to infect?
Pathogenesis - toxigenic diarrhea - no tissue invasion. Two types of toxins:
- heat-labile enterotoxin very similar to cholera toxin (same mechanism)
- heat-stable enterotoxin - small peptide toxin that activates guanylate cyclase, raising cGMP levels and leading to increased fluid secretion.
Must be able to colonize small intestine - express fimbrial adhesins- adhesion overcomes peristalsis effect.
What are the symptoms and treatment of EPEC infection?
Predominantly seen in infants less than 1yr (child care center outbreaks), occasional adult outbreaks. Large inocula needed.
Symptoms - watery stools, no blood or mucus. No tissue invasion. Vomiting, low grade fever common. May be prolonged, and relapse are common.
Treatment is to restore hydration. Usually responds rapidly to antibiotic therapy.
What is the pathogenesis of EPEC?
EPEC Pathogenesis - intimately adhere to enterocyte surface. A type III secretion system secretes the translocated-intimin receptor, initiating the characteristic “attaching and effacing lesion” - microvilli destruction, pedestal formation. This probably interferes with absorption leading to diarrhea.
What are the symptoms and treatment of EHEC?
b) Symptoms - 3-9 days of incubation; initial watery diarrhea, developing to grossly bloody liquid stools with abdominal cramps. Colonizes large intestine. Fever seen in more severe cases. Fecal leukocytes uncommon - important diagnostic feature.
c) Treatment - supportive, antibiotics have shown no proven benefit for prevention of HUS; usage may increase risk of HUS developing, do not decrease length or severity of diarrhea.
How is EHEC spread, what condition may it cause (other than diarrhea), and what is the major serotype?
Associated with food and water-borne outbreaks of bloody diarrhea and hemorrhagic colitis, leading to development of hemolytic uremic syndrome (HUS), mostly in young and
elderly. Major serotype is O157:H7; easily detected as colorless colonies on sorbitol(-) MacConkey media. Low infectious dose.
What is the pathogenesis of EHEC?
Pathogenesis - related to EPEC - form attaching-effacing lesions. EHEC strains produce one or both of Shiga-like cytotoxins Stx-I and Stx-II, chromosomally-encoded by lysogenic toxin-converting bacteriophages. Stx bind to Gb3 sphingolipids of enterocytes and renal endothelial cells. The internalized Stx A subunit binds to rRNA, inhibiting protein synthesis that results in tissue damage.
Is EHEC invasive?
No
Is ETEC invasive?
No
Is EPEC invasive?
No
