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Describe the general features of Enterobacteriaceae. what members of this family cause disease in humans?
- ubiquious - soil, water, vegetation, normal intestinal flora
- Gram negative, facultative anaerobic rods
- oxidase negative (no cytochrome oxidase; have other cytochromes to allow for ETC)
- members of family commonly associated with human disease:
- – Escherichia
- – Salmonella
- – Shigella
- – Yersinia
- – Klebsiella
- – Serratia
- – Proteus
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what is the best assay to help distinguish GI nL flora from the GI bacterial pathogens?
Lactose fermentation
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what are diagnostic tests for suspected traveler's diarrhea? describe the outcomes of the tests
- "Quick" biochem test to separate nL from pathogenic:
- To isolate G-:
- MacConkey
- --lactose + streaks will be purple; E.coli will "disperse" purple; lactose (-) is clear
- or Eosin-Methylene blue agar
- --"green sheen; black nucleated centers" = E coli (?)
- TSI = triple sugar iron assay (not routinely used) tests for:
- --lactose fermentation
- --glucose fermentation
- --H2S production
- --gas production
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how are ecoli serotypes grouped? Name the important serotypes for EHEC & ETEC.
- Serotypes based on surface Ag's:
- --O (lipopolysaccharide)
- --H (flagellar)
- --K (capsular)
- O157:H7 = EHEC
- O148:H28 = ETEC
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how do you separate the E. coli serotypes?
- E. coli Serotype differentiation via:
- immunologic assay
- culture on MacConkey agar w/sorbitol
- **E. coli O157:H7 does NOT ferment sorbitol (thus colonies are clear not pink)
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Describe the pathogenesis of ETEC in traveler's diarrhea.
- ETEC has 2 toxins clinically indistinguishable
- NON-invasive so, NO PMN's or RBC's in stool
- heat labile toxin (LT):--similar to cholera toxin (not as severe)
- --binds epithelial cells of SI
- --an A-B type toxin:
- "A" increases cAMP --> secretion Cl- and decrease absorption Na+ -->watery diarrhea
- heat stable toxin (ST):
- --increases cGMP (also affects Cl- secretion)
- = fluid hypersecretion; NO inflammation
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where are pathogenic strains of E. coli's virulence factors found? what are the virulence factors?
- found on:
- plasmids
- bacterio phages
- pathogenicity islands
- virulence factors:
- fimbriae
- secretion systems
- toxins
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describe the pathogenesis of an EPEC infection. what would be the presenting Sx's/signs?
- Enteropathogenic E. coli (EPEC):
- attchment & effacement via type III secretion system which alters the actin, then form pedestals
- --> descruction of surface microvilli
- STEPS in pathogenesis:
- 1. BFP (bundle forming pili): used for initial attachment to host cell
- 2. Secretion of bacterial factors: type III secretion systems--enter host cell & cause damages
- 3. bacteria releases factors that insert into host cell & allow for "infimate" attachment--see changes in host cell actin (formation of actin pedestals effacement damage) of host cell surface
- -->-->loss of mivrovilli
- S/Sx's:
- common in kids of developing countries
- fever
- diarrhea (infantile) b/c malabsorption of fluids
- V/N: hard to replace fluids
- non-bloody stools
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describe the pathogenesity of EHEC.
- aka STEC (shiga toxin-producing E. coli)
- found in U.S. (O157:H7 most diseases)
- -->cattle major reservoir (eat undercooked meat or unpasteurized fluids)
- produces Vero toxin (VTEC) = "shiga-like"
- --an AB-type; "A" inactivates 28S rRNA = stop protein synthesis -->death of epithelial cells
- low infectious dose, like shigella (~100cells)
- SORBITOL NON-fermenter on S-MAC
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what would be the presenting features of an EHEC infection?
- Hemorrhagic (hemorrhagic colitis):
- bloody, copious diarrhea
- few leukocyrtes
- usually self-limiting (~1wk)
- AFEBRILE
- in kids can cause hemolytic uremic syndrome (HUS):
- hemolytic anemia
- thrombocytopenia
- kidney failure
- 5-10% of kids infected w/EHEC
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what are features of EIEC? pathogenesis?
- persistant watery diarrhea (esp infants) >14d, can progress to dysentery
- may be as important as ETEC in traveler's D
- rare in U.S.
- common strains: O124, O143, O164
- invade & destroy colonic epithelium
- --replicates in cytoplasm
- --form "actin tail" allow spread b/w cells
- --Macrophages can also spread b/w cells
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what are the freatures of EAEC?
- persistent watery diarrhea >14d (esp. infants)
- also another cause of traveler's diarrhea
- bacterial fimbriae for attachment --> mucus&biofilm
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what are potential complications of taveler's diarrhea?
- increased risk for IBS
- yeast infection (?)
- dehydration, sepsis/shock
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what is the management of traveler's diarrhea?
- w/o systemic illness:
- Sxic w/ loperamide & rehydration
- +single dose ciprofloxacin, levofloxacin or ofloxacin cures most cases
- w/systemic or severe illness:
- 1000mg azythromycin
- or rifaximin
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what Sx's together are defined as dysentery?
- bloody diarrhea +/- mucus w/ PMNs & RBCs
- abd cramps
- tenesmus
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what is the most common cause of dysentery?
Campylobacter
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what are diagnostic tests of dysentery?
- Culture:
- Hektoen Enteric Agar:
- --Shigella will be transparent --> no CHO fermentation, no H2S production
- --Salmonella enterica will be BLACK (H2S producers) except Typhi is a weak H2S producer
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what are the major species of Shigella?
- S. dysenteriae--(grpA) MOST pathogenic
- S. flexneri--(grp B) common in developing cntry
- S. boydii--(grp C) india
- S. sonnei--(grp D) MOST common cause in industrial world, mildest
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what are the features of Shigella
- G- bacillus (rod), lactose-, NON-motile,H2S-
- genetically similar to Escherichia
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why is there a biphasic diarrheal illness in shigellosis?
- watery diarrhea precedes the dystenteric syndrome b/c of combined action of ShFT-1 enterotoxin resulting in active secretion & abnL water reabsorption.
- dysenteric syndrome is result of invasion of mucosa (Type III secretion system & actin filaments)
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what is the pathogenesis of shigella?
- direct fecal oral contamination
- *resistance to low-pH allows passage through GI (partly why only 100-200CFU required to cause infection)
- ShET-1 (shigella enterotoxin) causes watery diarrhea & mucosal inflammation --> invasion of mucosa
- encodes type III secretion system that inserts into membrane to allow effectors to transit --> bacteria induce their own uptake
- once inside, effectors trigger cytosckeletal rearrangements to further induce bacteria uptake
- intracellular shigellae use cytoskeleton to propel themselves inside infected cell --> allows cell-to-cell spread
- CK's released by infected cells attract more PMNs thus exacerbating the inflammation --> acute colitis
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describe features of Salmonella
- G- bacilli, lactose-, motile, H2S producer
- 2400 serotypes; based on:
- --somatic O ag (LPS outer sugars)
- --surface Vi an (only some) = capsule ag's
- --flagella H ag's
- Non-typhoid: more common
- --from poultry/eggs, dairy, & contaminated work surfaces
- Typhoid form is RARE in U.S.
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what is the pathogenesis of salmonella infection?
- ingestion contaminated food/water
- enters SI --> enters M cells --> basolateral surface
- Macrophages often ingest bacteria, but bacteria can prevents lysosomal enzymes of macrophage from degrading bacteria
- --bacteria disseminated by macrophages to liver, spleen, lymph nodes, bone marrow
- alters host cell (like shigella)
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describe the image:
- left: rectal luminal narrowing & mucosal inflammation (similar to UC)
- right: severe inflammatory infiltrate of PMNs & macrophages, glands are straight w/o architectural distortion or branching b/c it is ACUTE process
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describe biopsy of colon:
PMNs in lamina propria w/focal crypt destruction
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what are potential complications of dysentery?
- rectal prolapse
- perforation
- complications generally in kids <10yo:
- Hemolytic uremic syndrome
- thrombotic thrombocytopenic purpura
- microangiopathic anemia
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what is the management?
- Cipro = "best researched drug"
- avoid anti-motility agents b/c can precipitate toxic megacolon
- **don't forget to check Pum's drug document!
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