LECTURE - Diarrheagenic Escherichia coli (DEC) Flashcards
1 cause of traveller’s diarrhea
ETEC (enterotoxigenic)
a well as serious dehydration and death in infants
most common pathotype of E. coli
ETEC
Pathogenesis of ETEC
- attachment by different kinds of CFA (colonization factor antigen) pili (NOT the same as type 1 mannose sensitive pili found in almost all E. coli); attach to microvilli on enterocytes in small intestine
- toxin production (plasmid encoded)
> LT (labile toxin; can be denatured by heat; 56 degrees (pasteurization half an hour; AB5 toxin; complicated ribbon structure)
> ST (small, stable to heat so won’t denature)
most common cause of diarrhea in Egypt
ETEC
OBS
How LT of ETEC deregulate enterocyte in the small intestine
- toxins don’t kill enterocytes; just deregulate them (don’t absorb; secrete fluid instead)
- LT: binds to GM1 (ganglioside; same receptor as cholera); endosome; A subunit out => ADP ribosylates Gs protein which stimulates adenylate cyclase = formation of extra cAMP = release of Cl ions and absence of absorption so fluid builds up in lumen of gut
- voluminous diarrhea
these both cause bloody diarrhea in adults and potentially HUS in children
STEC and EHEC
This is implicated in Crohn’s disease
AIEC (adherent invasive E. coli)
Seven currently recognized pathotypes of E. coli
- Enteropathogenic E. coli (EPEC)
- Shiga toxin-producing E. coli
- Enteroaggregative E. coli (EAEC)
- Entertotoxigenic E. coli (ETEC)
- Diffusely-aggregative E. coli (DAEC)
- Adherent invasive E. coli]- Enteroinvasive E, coli (ETEC)
Most common of the seven pathotypes
ETEC
Another major cause of traveller’s diarrhea
EAEC
How ST of ETEC deregulate enterocyte in the small intestine
- toxins don’t kill enterocytes; just deregulate them (don’t absorb; secrete fluid instead)
- works through guanylate cyclase system; less notable but still important
- triggers production of more GMP
- same net effect as LT = lack of lfuid absorption and chloride secretion
- voluminous diarrhea
Besides decreased absorption, what else do LT and ST lead to??
- release of prostaglandins and leukotrienes
- affects nerves of GI (motility)
- stimulates cytokine production
Disease caused by EAEC
- persistent diarrhea in children
- traveller’s diarrhea with mucus
EAEC
Enteroaggregative E. coli
- aggregate on microvilli; effects on goblet cells through cytotoxins and enterotoxins ShET1, Pic, EAST1, Pet
- do NOT invade
- aggregation = biofilm formation
- stick to microvilli through aggregative adherence fimbriae (AAF)
- enteroaggregative [heat] stabile toxin
- pore-forming toxin (hemolysin) that increases Ca2+ influx into host cells
Preventative drugs for EAEC and ETEC
- bismuth subsalicylate (pepto bismol)
- antimicrobials (but not really good)
- Dukoral: oral vaccine against cholera with some ross-protection against LT (no help against ST though)
diseases caused by EPEC
- potentially fatal diarrhea in infants (and some traveler’s diarrhea in adults); mainly in developing countries
this is unique for EPEC
- binds to microvilli which causes them to distort into a pedestal
EPEC pathogenesis
- bundle-forming pili allow non-intimate binding (EAF plasmid)
- attaching and effacing (A/E) lesions are generated on the surface of the enterocyte by triggered by signal transduction events
- intimate binding through intimin and Tir leads to pedestal formation
= increased Ca2+ mobilization and phosphorylation of host proteins may cause cells to lose ability to absorb water
in EPEC organisms = LEE
locus of enterocyte effacement (LEE)
- eae (E. coli attaching effacing) genes are found on a PI in one of 5 operons (LEE-15)
STEC
Shiga toxin-producing E. coli; includes EHEC = enterohemorrhagic E. coli)
diseases caused by STEC
bloody diarrhea in adults, life-threatening hemolytic uremic syndrome (HUS) in children
Pathogenesis of STEC
- similar to EPEC but adhesins are different and STEC also produces an A-B toxin called Stx1 (Shiga-like toxin) aka ‘verotoxin’ and/or Stx2 encoded by a bacteriophage
- affects kidney cells
Stx 1 and 2 of STEC
- AB5 structure
- A = N-glycosidase catalytic activity; acts by removing a specific adenine base from the 28 S rRNA of the 60 S ribosomal subunit within infected cells (adenine important for elongation factor binding)
= stops protein synthesis
= LETHAL in enterocytes; cytotoxic does not just deregulate
diseases caused by DAEC
UTI and complications of pregnancy
- sometimes diarrhea, esp. in children >12 mos old
pathogenesis of DAEC
(diffusely aggregative E. coli)
- binding of unique “Dr” fimbrial adhesins (receptor DAF - decay-accelerating factor, CD55) promotes the formation of cell membrane extensions
- other virulence factors cause alteration of intracellular signaling and inflammation
- don’t form biofilms
- coiling of microvilli when they attach but don’t typically invade
AIEC
adherent invasive E. coli
diseases caused by AIEC
implicated in Crohn’s disease
pathogenesis of AIEC
- colonizes the intestinal mucosa of patients with Chron’s disease and is capable of invading epithelial cells s well as replicating within macrophages
- uses type I pili to adhere to intestinal cells ad long polar fimbriae contribute to invasion
- can cause granulomas
