Term
| what are some characteristic features of Enterobacteriaceae? |
|
Definition
-gram negative
-facultative anaerobe
-usually motile
-live in gut
-can distinguish different species by biochemical tests |
|
|
Term
| T/F: Shigella has a flagella for motility |
|
Definition
| F: Shigella mobilizes host actin in a mechanism similar to that of Listeria |
|
|
Term
|
Definition
| specific antigens in the LPS of the cell wall; used to classify species |
|
|
Term
| T/F: E. coli is the most abundant facultative anaerobe in normal feces. |
|
Definition
| T: remember that E.coli is an abundant colonizer of the human gut; most are NOT pathogenic, only a few strains cause diarrheas and other disease |
|
|
Term
| is vibrio cholera part of the normal flora? |
|
Definition
| NO...naturally found in coastal estuarine waters, associated with phytoplankton. |
|
|
Term
| what are some benefits conferred by the E.coli that are part of our natural flora? |
|
Definition
-contribute to colonization resistance against other pathogenic organisms like C. difficile
-produce beneficial metabolites |
|
|
Term
what are some of the diverse diseases that E. coli can cause?
what is the basis for this diversity? |
|
Definition
-dysentery (bloody diarrhea)
-diarrhea
-hemolytic uremic syndrome
-UTIs
-meningitis
*horizontal DNA transfer via transposons, pathogenicity islands, phages, and plasmids |
|
|
Term
| name some members of the Enterobacteriaceae family |
|
Definition
-escheria
-proteus
-shigella
-salmonella
-yersinia
-klebsiella
-enterobacter
-serratia |
|
|
Term
| what are the 6 diarrheagenic species of e. coli? |
|
Definition
-enterotoxigenic (ETEC)
-enteropathogentic (EPEC)
-enterohemorrhagic (EHEC)
-enteroaggregative (EAEC)
-enteroinvasive (EIEC)
-diffuse adhering (DAEC) |
|
|
Term
| compare the adherence and pathogenic factors of ETEC and EPEC: |
|
Definition
-adherence:
ETEC: CFA - colonization factor antigens
EPEC: BFP - bundle forming pilus
-pathogenicity:
ETEC: heat-labile and heat-stable enterotoxins
EPEC: uses type III secretion system to express attaching and effacing proteins |
|
|
Term
| what is the role of the ETEC's CFAs? |
|
Definition
| CFA - group of fimbriae that bind oligosaccharides on host tissues and confer tissue specificity; REQUIRED FOR VIRULENCE |
|
|
Term
| is our immune system effective against CFAs? |
|
Definition
| -CFAs are recognized by our immune system, but they vary widely in structure and antigenicity, so immunity is type specific |
|
|
Term
name the e. coli species associated with each of the following adherence structures:
-CFA
-P pili
-BRP |
|
Definition
CFA = ETEC
P Pili = UPEC (remember UTIs?!)
BFP = EPEC |
|
|
Term
| how does ETEC cause diarrhea? |
|
Definition
-heat-stable and -labile enterotoxins; A-B toxins
1. AB toxin endocytosed; 2. A subunit released into cytoplasm via channel formed by B; 3. A subunit ADP-ribosylates adenylate cyclase and turns it constitutively ON; 4. get TONS of cAMP; 5. Na+ reabsorption decreases, Cl- efflux increases; 6. increased osmotic pressure outside cell causes fluid to leave cell --> DIARRHEA |
|
|
Term
| what makes heat stable toxins stable? |
|
Definition
|
|
Term
| what other diarrheagenic toxin has a similar pathogenicity to ETEC's toxins? |
|
Definition
| cholera toxin is also an ADP ribosylase that increases cAMP |
|
|
Term
| which pathogens are characterized by causing watery diarrhea with no epithelial damage? |
|
Definition
|
|
Term
| Why does ETEC have pathogenic properties that other e. coli do not? |
|
Definition
| -has acquired a plasmid with virulence factors: CFAs, heat-labile and heat-stable enterotoxin encoded on plasmid |
|
|
Term
| where in the genome are EPEC's virulence factors encoded? |
|
Definition
-BFP: plasmid encoded *required for virulence*
-attaching and effacing proteins - type III secretion system on pathogenicity island, locus of enterocyte effacement (LEE) |
|
|
Term
| what proteins are found on the EPEC LEE? |
|
Definition
-LEE = locus of enterocyte effacement * REQUIRED for VIRULENCE*
-41 genes
-type III secretion system
-secretion proteins
-Intimin/Tir Adhesion/Receptor pair |
|
|
Term
| how are pathogenicity islands identified as being from a distinct origin from the rest of the e. coli genome? |
|
Definition
|
|
Term
what is the type III secretion system?
where is it encoded? what is the function of the secreted factors in EPEC? |
|
Definition
-type III secretion systems use a needle like apparatus that spans the bacterial membranes and the host membrane to inject factors directly into the host cell cytoplasm
-encoded on LEE
-used to secrete factors that facilitate attachment (Tir/intimin receptor) and effacement |
|
|
Term
| what signals the assembly and action of the type III system in EPEC? |
|
Definition
|
|
Term
| the formation of a pedestal is associated with which e. coli species? what is the mechanism behind pedestal formation? |
|
Definition
-EPEC
-polymerization of actin forms protruding pedestal from cell membrane |
|
|
Term
| what are the 3 major steps in EPEC pathology? how does it cause diarrhea? |
|
Definition
1. initial adherence to small bowel epithelial cell mediated by BFP; 2.type III secretion system delivers a membrane receptor protein, Tir, and other effectors to the host cell. 3. intimin on the bacterial surface mediates intimate adherence to the cell by binding to Tir receptors. Polymerization of actin and other host cytoskeletal proteins is induced, and rearrangements of the cytoskeleton occur. Together these processes result in the characteristic EPEC pedestal.
-diarrhea is thought to be a result of the malabsorption due to damaged villi and disruption of epithelial tight junctions |
|
|
Term
| what makes EHEC so contagious? |
|
Definition
| -it has a low inoculum (<100 cfu) due to its acid resistance, so it can spread more easily from person to person |
|
|
Term
| what are the reservoirs of EHEC? if were an EHEC outbreak of spinach, how would the spinach get contaminated? |
|
Definition
-reservoirs: cattle, contaminated food and water
-is FECAL-ORAL transmission, so spinach probably got contaminated with cow manure had EHEC in it |
|
|
Term
| what is the major serotype of EHEC found in the US? |
|
Definition
|
|
Term
| how can you distinguish EHEC from other e. coli species using culture? |
|
Definition
| it is lac fermenting and sorbitol non-fermenting |
|
|
Term
| what are the virulence factors of EHEC? |
|
Definition
| forms attaching and effacing lesions, plasmid hemolysin, and produces shiga toxin (inhibits protein synthesis, can go systemic) |
|
|
Term
| what is the mode of action of the shiga toxin? |
|
Definition
| cleaves adenosine in 23S rRNA (60S subunit of human ribosome) -> no protein synthesis, cell death |
|
|
Term
| what is the effect of Norfloxacin on EHEC? |
|
Definition
| -INCREASES toxin release; DON't use Abx for EHEC |
|
|
Term
| what other e. coli species is EHEC most closely related to? |
|
Definition
| the EHEC serotype, O157:H7 evolved from EPEC |
|
|
Term
| what other e. coli species is EHEC most closely related to? |
|
Definition
| the EHEC serotype, O157:H7 evolved from EPEC |
|
|
Term
| which species of e. coli is associated with persistent diarrhea in children and with patients with HIV? |
|
Definition
| EAEC - enteroaggregative e. coli |
|
|
Term
| what are some of EAEC's distinguishing virulence factors? |
|
Definition
-aggregative adherence mediated by plasmid-encoded fimbriae; forms BIOFILMS
-damage to intestinal cells
-toxins |
|
|
Term
| which two diarrheagenic species exhibit intracellular cell to cell spreading? |
|
Definition
|
|
Term
| if you do a stool culture on MacConkeys, what are you testing for? what diarrheagenic species would give you a positive test? which would give you negative? |
|
Definition
-testing for lactose fermentation
-Lac + (pink, red): e. coli species
-Lac - (yellow): salmonella, shigella |
|
|
Term
| what is the invasion machinery of EHEC and Shigella? where are these gene encoded? |
|
Definition
| -type III secretion system encoded on pathogenicity island |
|
|
Term
| if you grew pink colonies on MacConkey's from a stool sample and you suspected EHEC, what further testing could you do? |
|
Definition
| -sorbitol testing: EHEC is the only sorbitol- e coli species; or could test for shiga/verotoxin |
|
|
Term
| what are the microbiological characteristics of shigella? |
|
Definition
-part of enterobacteriaceae family
-gram negative enteric rod
-most do not ferment lactose
-non-motile |
|
|
Term
| what are the four species of Shigella? |
|
Definition
-s. sonnei
-s. flexneri
-s. dysenteriae
-s. boydii |
|
|
Term
| which species of shigella would you expect to be the cause of an explosive outbreak? |
|
Definition
|
|
Term
| which species of Shigella would you be most likely to get while traveling outside the U.S.? which is more common in the U. S.? |
|
Definition
-s. flexneri - worldwide
-s. sonnei - US |
|
|
Term
| T/F: E. coli and Shigella share the same modes of transmission. |
|
Definition
| F: shigella has NO animal reservoirs so and has low infectious dose so can more easily be transmitted human to human (fecal-oral) |
|
|
Term
| how is Shigella's site of entry different from that of e. coli? what are the steps in Shigella's entry? |
|
Definition
-Shigella enters M cells, not villous epithelial cells
1. crosses lumenal side of M cells; 2. exits basolateral side of M cell; 3. is taken up by macrophages; 4. causes mac lysis -> shigella escapes; 5. enters basolateral side of epith, creating a "splash"; 6. can spread to neighboring cells intracellularly |
|
|
Term
| how does Shigella accomplish intracellular cell-cell spread? |
|
Definition
| -nucleates actin using VirG; can protrude out of cell into neighboring cell cytoplasm; uses hemolysin to break thru membranes |
|
|
Term
| what is the difference between apoptosis and pyroptosis? what causes pyroptosis? |
|
Definition
-apoptosis is a slow, non-inflammatory cell death mechanism in which cells stay in tact
-pyroptosis is a rapid, inflammatory form of cell death with leaky cells and induction of IL-1B, IL-18.
-Shigella induces pyroptosis and apoptosis as well as necrosis |
|
|
Term
| where is the site of Shigella infxn? |
|
Definition
|
|
Term
| which of the e. coli species cause watery diarrhea? which cause bloody diarrhea? |
|
Definition
watery: ETEC, EPEC, EAEC
bloody: EIEC, EHEC |
|
|
Term
| salmonella, like most other diarrheagenic species, is a gram negative rod. what features are useful for distinguishing it from other organisms? |
|
Definition
-lactose negative
-H2S producing |
|
|
Term
| what types of diseases are caused by s. typhimurium? by s. typhi? |
|
Definition
-typhimurium: focal systemic infxns (i.e. endocarditis, osteomyelitis)
-typhi: typhoid fever - systemic, with bacteremia, damage |
|
|
Term
| T/F: salmonella has multiple pathogenicity islands and two Type III secretion systems. |
|
Definition
|
|
Term
| why is S. typhi able to cause more systemic infxn than S. typhimurium? |
|
Definition
| -can blunt local immune response that usually contains infection to gut; instead can go systemic |
|
|
Term
| how do our immune system recognize and respond to salmonella? |
|
Definition
-TLR5 binds flagella
-TLF4 binds LPS
-innate immunity is triggered; also activates adaptive immune response |
|
|
Term
| which serotype of salmonella enterica causes diarrhea? what is the pathogenesis? |
|
Definition
-typhimurium (non-typhoid)
-type III secretion system, LPS, flagella trigger inflam response
-host response causes fluid loss and damage |
|
|
Term
| T/F: only s. typhi is invasive |
|
Definition
| F: all salmonella are invasive and inflammatory |
|
|
Term
| which serotype of Salmonella has a capsule? |
|
Definition
|
|
Term
| what types of people are more likely to become salmonella carriers? why? |
|
Definition
-people with gallstones
-salmonella can adhere; prevents flushing |
|
|
Term
differentiate between:
food poisoning
gastroenteritis
colitis |
|
Definition
-food poisoning: usu involves ingestion of pre-formed toxin; sometimes produced in gut after ingestion of microbes
-gastroenteritis: infection of UPPER GI, mostly small bowel/upper tract (or used for all infectious diarrhea)
-colitis: infection primarily of colon; lower tract disease |
|
|
Term
| what sx are associated with upper tract disease? with lower tract? |
|
Definition
-upper: cramps, (watery) diarrhea, vomiting, pain, NO WBCs
-lower: inflammatory/bloody diarrhea, WBCs |
|
|
Term
| what are some signs of dehydration? |
|
Definition
-poor skin turgor
-dry tongue, axilla
-lethargy, confusion |
|
|
Term
| what kind of dx tests would you do to determine the cause of diarrhea? |
|
Definition
-microscopic: presence of WBC in colitis
-culture: for specific bacterial pathogens
-detection of antigen
-detection of toxins (i.e. Shiga toxin)
-check for ova or parasites |
|
|
Term
| what non-bacterial causes of diarrhea should also be part of your differential? |
|
Definition
| -inflammatory bowel disease; can do GI endoscopy, biopsy if you suspect IBD |
|
|
Term
| what are 3 usual pathogens that cause food poisoning? at what point do they make their toxin, before or after ingestion? |
|
Definition
-staph aureus - heat stable enterotoxin A; produced IN VITRO
-bacillus cereus - several heat stable toxins produced IN VITRO
-clostridium perfringens - toxin produced IN VIVO, after ingestion |
|
|
Term
| what are the major host defenses against infxn by enteric organisms; what can compromise the integrity of each of these defenses? |
|
Definition
gastric acidity
-some acid pathogens are acid-resistant: Shigella, EHEC, norovirus, rotavirus
-acid decreases with age, use of antacids, H2 blockers, proton pump inhibitors mucus, stomach resection, vagotomy
intestinal motility
-some meds decrease peristalsis
normal flora
-use of Abx can wipe out normal flora and let other pathogens colonize
local antibody - secretory IgA
PMNs and macrophages |
|
|
Term
| how can you prevent toxin production by staph aureus and bacillus cereus? |
|
Definition
-refrigeration, good sanitation
*HEAT does not prevent toxin - both organisms produce heat stable toxins |
|
|
Term
| how can you distinguish food poisoning from gastroenteritis? |
|
Definition
-short incubation period: 2-6 hrs
-explosive onset
-nausea and vomiting prominent; diarrhea not always a factor, and dehydration and hypokalemia also not usually problems |
|
|
Term
| what virus is a double stranded naked RNA virus and is the most common cause of infectious diarrhea in kids 6-24 months? |
|
Definition
|
|
Term
| would you be more likely to get infected with norovirus from lettuce or chicken soup? |
|
Definition
| -lettuce; it is heat-labile so properly cooked foods should kill virus |
|
|
Term
| what are the two vaccines for rotavirus, and what are the characteristics of each? |
|
Definition
-Rotarix: human live, attenuated virus; monovalent (Glaxo-Smith-Kline) - CURRENTLY OFF THE MARKET, but used historically
-RotaTeq: human/bovine recombinant vaccine; pentavalent (Merck) |
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