LECTURE - Diarrheagenic Escherichia coli (DEC)

Question 1

1 cause of traveller’s diarrhea

Answer 1

ETEC (enterotoxigenic)

a well as serious dehydration and death in infants

Question 2

most common pathotype of E. coli

Answer 2

ETEC

Question 3

Pathogenesis of ETEC

Answer 3

• 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)

Question 4

most common cause of diarrhea in Egypt

Answer 4

ETEC

OBS

Question 5

How LT of ETEC deregulate enterocyte in the small intestine

Answer 5

• 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

Question 6

these both cause bloody diarrhea in adults and potentially HUS in children

Answer 6

STEC and EHEC

Question 7

This is implicated in Crohn’s disease

Answer 7

AIEC (adherent invasive E. coli)

Question 8

Seven currently recognized pathotypes of E. coli

Answer 8

1. Enteropathogenic E. coli (EPEC)
2. Shiga toxin-producing E. coli
3. Enteroaggregative E. coli (EAEC)
4. Entertotoxigenic E. coli (ETEC)
5. Diffusely-aggregative E. coli (DAEC)
6. Adherent invasive E. coli]- Enteroinvasive E, coli (ETEC)

Question 9

Most common of the seven pathotypes

Answer 9

ETEC

Question 10

Another major cause of traveller’s diarrhea

Answer 10

EAEC

Question 11

How ST of ETEC deregulate enterocyte in the small intestine

Answer 11

• 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

Question 12

Besides decreased absorption, what else do LT and ST lead to??

Answer 12

• release of prostaglandins and leukotrienes
• affects nerves of GI (motility)
• stimulates cytokine production

Question 13

Disease caused by EAEC

Answer 13

• persistent diarrhea in children

- traveller’s diarrhea with mucus

Question 14

EAEC

Answer 14

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

Question 15

Preventative drugs for EAEC and ETEC

Answer 15

• 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)

Question 16

diseases caused by EPEC

Answer 16

• potentially fatal diarrhea in infants (and some traveler’s diarrhea in adults); mainly in developing countries

Question 17

this is unique for EPEC

Answer 17

• binds to microvilli which causes them to distort into a pedestal

Question 18

EPEC pathogenesis

Answer 18

• 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

Question 19

in EPEC organisms = LEE

Answer 19

locus of enterocyte effacement (LEE)

- eae (E. coli attaching effacing) genes are found on a PI in one of 5 operons (LEE-15)

Question 20

STEC

Answer 20

Shiga toxin-producing E. coli; includes EHEC = enterohemorrhagic E. coli)

Question 21

diseases caused by STEC

Answer 21

bloody diarrhea in adults, life-threatening hemolytic uremic syndrome (HUS) in children

Question 22

Pathogenesis of STEC

Answer 22

• 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

Question 23

Stx 1 and 2 of STEC

Answer 23

• 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

Question 24

diseases caused by DAEC

Answer 24

UTI and complications of pregnancy

- sometimes diarrhea, esp. in children >12 mos old

Question 25

pathogenesis of DAEC

Answer 25

(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

Question 26

AIEC

Answer 26

adherent invasive E. coli

Question 27

diseases caused by AIEC

Answer 27

implicated in Crohn’s disease

Question 28

pathogenesis of AIEC

Answer 28

• 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