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45 Cards in this Set
- Front
- Back
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Classification of E.coli strains |
1.Serotyping-reactivity of surface Ags to Abs (OH, K) 2. Virotyping: based on virulence factors 3. Adherence: localized adherence, brick, diffuse 4. phylotype: based on phenotypic characteristics
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Serotyping classification |
Serotyping-reactivity of surface Ags to Abs( E.coli O157:H7 -O = O Ag of LPS - 160 serogroups -H = hauch = flagellum
also K= capsular Ag(K1: leading G- bacteria causing neonatal meningitis) |
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Common virotypes |
ETEC:enterotoxigenic EAEC: enteroaggregative EPEC: enteropathogenic EHEC: enterohemorrhagic EIEC: Enteroinvasive DAEC: diffusely adhering UPEC: Uropathogenic AIEC: adherent/invasive |
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Virulence factore Stanley Falkow's postulate |
1. gene present in strains that cause disease 2. not present in avirulent strains 3. disruption reduces virulence 4. reintroduction restores virulence 5. expressed during infection 6. host Specific immune response to gene protects host |
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How E.coli acquire VF |
1. gain of genes from mobile genetic elements -plasmids: ETEC toxins -transposons: ETEC heat stable toxin (ST) -pathogenecity islands: EPEC, EHEC -bacteriophages: EHEC Shiga toxin (Stx) 2. black holes: loss of genes that leads to increased virulence |
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Genome sequences of pathogenic E.coli |
they have more genes than non-pathogenic E. coli |
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Pathogenesis of different E. coli virotypes |
EPEC EHEC ETEC EAEC EIEC DAEC |
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ETEC: enterotoxigenic E.coli Overview |
-Water diarrhea in kids and older individuals who have not been exposed previously -traveller's diarrhea - Adhere to intestinal mucosa - Non-invasive, produces toxin that act on mucosal cell to cause diarrhea. |
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ETEC: adherence, toxin |
CFAs(colonization factor antigens) -fimbriae, CFA I/II/III/IV associated w/ human diseases(20 total)
Toxins(may have either one or both): 1. heat-labile (LT) B binds GM1 ganglioside surface receptor -AB5, related to cholera toxin -A: ADP-ribosylates --> G protein -increase Cl- secretion -->inhibits NaCl absorption --> diarrhea 2. heat-stable (ST) - first precursor (72AA), need to be cleaved to be mature (17AA) |
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ETEC: therapy |
-Oral rehydration -Illness is self-limiting |
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EAEC: enteroaggregative Overview |
-persistent diarrhea in children and AIDS patients -Traveler's diarrhea -resemble ETEC in response to antibiotics and clinical presentations. - AAF(aggregative Adherence Fimbriae) bind to small intestine --> form clumps(Stacked brick appearance) -non-invasive, produces toxins
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EAEC:adhesion, toxins |
Adhesin: Aggregative Adherence Fimbriae (AAF) -Non-invasive, produce toxins
Produces a lot of toxins, highly heterogenous Toxins |
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EIEC: enteroinvasive overview |
EIEC resembles shigella. -causes dysentery: abdominal cramps, diarrhea, vomiting, fever, chills, malaise. - dose less than 10 organisms to infect. - No toxins! |
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EIEC pathogenesis |
- no toxins - invasion, escape from vacuole, actin-based motility, cell-cell spreading.
pWR100 virulence plasmid of EIEC and shigella: -encodes T3SS. -Invasion into host cells requires T3SS |
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Shigella invasion |
Involves multiple T3SS effectors, tyrosine kinase signaling and Rac/Rho(actin motility) -rho regulates actin organization
1. internalization 2. burst vacuole using T3SS, ipgD 3.membrane fragments of vacuole acts as DAMPs, triggers host cell signalling responses including cytokine production, autophagy, pyroptosis. |
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EIEC/shigella actin motility |
IcsA from pWR100 binds and activates N-WASP -expressed at one pole of bacteria, actin polymerization provides motility |
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EPEC |
-Major cause of neonatal diarrhea, most commonly affects child -can infect many types of cell because it secretes its own receptor in target 3 stages of host cell interaction 1. Non intimate binding -bundle forming pili(Bfp) 2. Type 3 secretion: secrete Tir in cell (receptor for EPEC) 3. intimate binding -pedestal formation: host cell bulges out, bacteria attached to the "mountain" |
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EPEC: Pedestal formation |
Locus for Enterocyte Effacement pathogenicity island: 1. a T3SS 2. Tir effector -inserted in host plasma membrane in hairpin configuration. Binds intimin on bacteria 3. outer membrane protein Intimin(binds Tir) |
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EPEC: disruption of tight junctions |
-depend on T3SS -several effectors, knockout any of them abolish TJ disruption |
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EPEC: how does it cause disease |
1. effacement of microvilli(loss of absorptive surface) 2. disrupt tight junctions 3. signal transduction in host cells 4. alterations in water and electrolyte absorption and secretion |
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EHEC: enterohemorrahagic overview |
-recently emerged -EPEC strain acquired Shiga toxin(S. dysenteriae) via bacteriophage -note : EIEC do not code Shiga. |
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EHEC:"Hamburger disease" |
- cattle are major reservoir of EHEC, asymptomatic carriers - associated with ground beef, manure, water
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EHEC pathogenicity islands |
1.3 Mb specific to EHEC compared to K12 |
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EHEC pathogenesis |
Similar to EPEC -LEE pathogenicity island -T3SS -Tir(pedestal formation) -tight junction disruption
Different to EPEC -Shiga toxin -in colon(not small intestine) |
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EHEC: Shiga toxin |
AB toxins Stx1 and Stx2 -encoded by bacteriophage, integrated in chromosome(prophage) -B binds Gb3 -GB3 present in - intestinal epithelium, kidney, neurons, not in cattle. -A inhibit translation by modifying 60S subunit |
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EHEC: pedestal formation (different from EPEC) |
EPEC: Nck binds N-WASP and recruit actin machinery to -Tir in order to support it. -Nck - cells -> no pedestal in EPEC, EHEC pedestal not affected
EHEC tir is not tyrosine phosphorylated -requires other EHEC-encoded factors to work: expressed EHEC Tir alone in EPEC Tir-/- mutant still no pedestals. -EspFu important for pedestal formation -activates N-wASP: competition binding with CDC42 for GTPase binding domain allowing N-WASp to be active.
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Linking between EspFu and Tir |
Host protein IRSp53/Irtks |
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EHEC illness |
- hemorrhagic colitis: watery diarrhea followed by bloody d. -10 organisms enough for infection -10% develop hemolytic uremic syndrome(HUC) -renal failure -decrease in platelets - HUC: chronic renal problem -HUC: neurological problem - 3-5% fatal |
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Treatment/prevention of EHEC |
-use of Antibiotics controversial(induction of toxin) -rehydration therapy -handwashing -thorough cooking of hamburger meat
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E.coli O104:H4 overview |
Bloody diarrhea in germany stx+(shiga toxin) intimin-: not EHEC resistance to 3rd generation cephalosporines
-highthroughput sequencing -Crowd-sourcing for bioinformatin analysis 24hours after release of data, genome assembled |
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E.coli O104:H4 |
atypical strain -share some features EHEC but: shiga toxin, T3SS negative -Resembles EAEC -EAEC: used to be Shiga-toxin negative
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E. coli O104: H4 outbreak |
largest E.coli outbreak to date 3842 cases, 855 HUS, 53 deaths -median age: 42 years old, 68% HUS women -linked to sprouts |
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ExPEC: extraintestinal E.coli infections |
-Urinary tract infections -meningitis -sepsis -Extraintestinal pathogenic E.coli: ExPEC |
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UTI by E.coli |
large proportion of both community acquired and hospital acquired are caused by E.coli
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Community acquired UTIs |
80% are women. caused by UPEC(6 serogroups) 1/3 of women will atlease have 1 UTI -recurrent infection common |
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UPEC pathogenesis |
Colonize bowel first(no symptoms) then move to urethra - distance between colon and urethra smaller in women. Vaginal tract can be colonized too - Foodborne(poultry for example) -Ascending infections(from trivial to severe) 1. urethritis 2. cystitis ... 3. sepsis |
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Hospital acquired UTIs |
Catherization a major risk factor - 1 million cases annually can also be descending infections (from bloodstream) |
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Virulence factors of UPEC |
heterogenous, can have a range of virulence factors 1. adherence factors 2. toxins 3. nutrition -Iron: siderophore + heme 4. LPS, capsule - capsule prevents phagocytosis - LPS --> host response, may cause symptoms but necessary for clearance.(TLR4 -/- asymptomatic but carrier) |
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UPEC adhesins |
major virulence determinant of UPEC -major defense vs UPEC = flushing action of urine
2 main adhesins 1. type 1 fimbriae --> bladder 2. Pap pili --> to kidney(pyelonephritis-associated pilus) PAP pili associated strains more resistant to AMPs |
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Cranberry juice and UPEC infection |
- fructose inhibits adherence of type - 1 fimbriated E. coli uro cell - proanthocyanidins inhibit adherence of P-fimbriated E. coli to uro cell |
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UPEC invasion: uroepithelium |
UPEC makes Uroepithelial cell shed skin Some UPEC inside: -latent phase of infection -not actively dividing -highly resistant to beta-lactam -can reactivate(recurrent infection)
consider antibiotic therapy |
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Meningitis and other disseminated infections |
E.C leading cause of infant meningitis -case fatality 15-40%. severe neurological defects in many survivors -80% are K1, many serotypes -from blood to CNS |
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causes of E.coli septicimia |
-intestinal perforation -Ascending UTIs -E.coli lung infections in ventilator patients |
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Virulence factors for meningitis and septicemia |
-K1 capsule: antiphagocytic, serum resistance -LPS-> septic shock -CNF-1--> requiref dor invasion |
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Compare K1 and non-pathogenic strain |
-22 genomic islands only present in K1 -deletion of 9 of the islands decrease virulence |
