|MIM 425: Lecture: Gram Negative Rods of the Enteric Tract||
Rm E706 MSB
|8:30-9:20 Room 423CMW||
Tel: X 6-5600 E-mail: firstname.lastname@example.org
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Gram negative rods can infect many sites in the body including the enteric tract, respiratory tract, or as opportunistic infections of various sites such as urinary tract, peritoneum and wounds. These organisms provide models for many mechanisms of pathogenesis: attachment to host cells, invasion of host cells, toxin production, exchange of pathogenic factors.
Frequent causes of enteric infections: Salmonella, Shigella, Campylobacter
Less frequent: Escherichia, Vibrio, Yersinia
Frequent UT infections: Escherichia (especially female)
Less frequent: Enterobacter, Klebsiella, Proteus, Pseudomonas
Vibrio cholerae: comma shaped, oxidase positive. human carriers, fecal contamination. Causes large volume, watery diarrhea: rice-water stool. No blood. If fluid and salts not replaced get cardiac and renal failure. 40% mortality without treatment. >106 organisms required for infection. Attaches to small intestine and produces toxin. Mechanism of toxin- A-B toxn. increased cAMP levels causes loss of electrolytes.
Enterobaceriaceae: many found in colon. Facultative anaerobes, ferment glucose, oxidase negative
Escherichia coli: many serotypes, some part of natural flora of large intestine (Bacteroides primary inhabitant). Use tests for the presence of "coliforms" as a measure of fecal contamination in water since these organisms not free-living.
Antigens: O= wall (LPS); H= flagella; K= capsular; thousands of serotypes.
Different pili help determine host specificity- UT or GI, neonate or adult. Invasive strains cause bloody diarrhea.
Five different types based on pathogenesis- see tables.
ETEC- enterotoxigenic, After attachment, two types of enterotoxins produced by certain toxigenic strains. LT and ST toxins, ent transmissible plasmid, ST a transposon.
Heat-labile toxin (LT) stimulates adenyl cyclase similar to cholera toxin- causes release of K, Cl, fluid. Heat-stable toxin (ST) stimulates guanylate cyclase. These strains dont invade or cause inflammation- watery diarrhea. Specific pili in certain strains can cause infections in newborns
EHEC- enterhemoragic, hemorrhagic colitis- bloody diarrhea. E. coli O157 H7 acquired from contaminated food (especially undercooked hamburger)- bloody diarrhea with no inflammation (no white cells). Causes HUS Hemolytic Uremic Syndrome: acute renal failure often fatal. Shiga toxin (SLT-1 and 2) SLT-1: A-B toxin binds glycolipid of microvillus membrane. Shuts down protein synthesis by inactivating ribosomes- cleaves 28s rRNA- no longer binds EF-1
EIEC- very similar to Shigella- invasive. Invasin same as Shigella, on same plasmid.
EPEC- major cause of infant diarrhea. Plasmid encodes eae- EPEC adherence factor. Mechanism of attachement- see movie. Effacing lesion (eae gene), injection of receptor, pedestal formation.
Capsule and endotoxin prominent role in systemic infections- neonatal meningitis, urinary tract infections, sepsis. Leading cause of UTI, both community and nosocomial.
Salmonella: most common cause of bacterial enterocolitis in US. Also causes typhoid fever
S. enterica major species- almost all previous species now serotypes.
Enterocolitis: food contamination especially poultry and eggs (mayo). Pets (turtles). Req. ³105 organisms. Incubation: 6-48 hr. nausea and vomiting, then abdominal pain and diarrhea. Self-limited to a few days. Most common cause S. enteritidis-typhimurium.
invasion of tissues- inflammation and diarrhea.
Typhoid: caused by S. enterica ser. typhi. Slow onset, fever. After 1 week get bacteremia- high fever, delirium, tender abdomen, enlarged spleen. Resolves in 3 weeks, may cause intestinal damage. Can become chromic carrier. Vaccine available, but only moderately effective.
Shigella: Fecal-oral spread. Less than 100 organisms req. for infection. Incubation: 1-4 days. Fever, cramps, diarrhea- later with blood. S. dysenteriae severe, long lasting, usually travelers; S. sonnei, milder disease in US. Unlike salmonella dont enter blood stream even though invade GI cells.
Helicobacter: Urease positive. Causes gastritis and is major cause of peptic ulcers, risk factor for gastric carcinoma. Produces large amount of ammonia that protects it from stomach acid.
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