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21 Cards in this Set
- Front
- Back
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Shigella
Species/serogroups A: S. ________; rare in U.S.; most severe B: S. _______; native american pops. and developing countries C: S. _____' rare D: S. ______; most common in U.S. and developing countries Very closely related to E. coli … but, ________ normal gut flora! |
Species/serogroups
A: S. dysenteriae; rare in U.S.; most severe B: S. flexneri; native american pops. and developing countries C: S. boydii; rare D: S. sonnei; most common in U.S. and developing countries Very closely related to E. coli … but, NOT normal gut flora! |
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Shigella –cont.
Diseases: Wide range: asymptomatic to __________ HUS is a complication (re: Shiga toxin) Pathogenesis: Transit through _________ (refractory to low pH) Transient multiplication in ____________ Invasion of _____ __________ Cell to cell spread |
Diseases:
Wide range: asymptomatic to bloody diarrhea HUS is a complication (re: Shiga toxin) Pathogenesis: Transit through stomach (refractory to low pH) Transient multiplication in small intestine Invasion of colonic epithelium Cell to cell spread |
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Cellular Pathology of Shigellosis
Release from dead cells into ________ propria and reinvasion through basolateral surface of epithelial cells Direct passage between cells w/o exposure to extracellular environment Bacteria-generated protrusions “Fireworks” -A. T. Maurelli, 1999 |
Release from dead cells into lamina propria and reinvasion through basolateral surface of epithelial cells
Direct passage between cells w/o exposure to extracellular environment Bacteria-generated protrusions “Fireworks” -A. T. Maurelli, 1999 |
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Shigella Virulence Factors
Most virulence factors on large virulence plasmid (Identical in E_EC) Invasion plasmid antigens (IPAs A - D) - is this invasive? (yes) Induce ____________ in epithelial cells Transported by a _____ – mxi and spa genes VirG: facilitates intercellular spread Chromosomal determinants Luc: _________ – iron scavenging (siderophore) Stx: ____ toxin – inhibits host ______________ Binds to vascular endothelium Expression induced by low ____ |
Most virulence factors on large virulence plasmid (Identical in EIEC)
Invasion plasmid antigens (IPAs A - D) Induce phagocytosis in epithelial cells Transported by a TTSS – mxi and spa genes VirG: facilitates intercellular spread Chromosomal determinants Luc: aerobactin – iron scavenging (siderophore) Stx: Shiga toxin – inhibits host protein synthesis Binds to vascular endothelium Expression induced by low Fe++ |
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Shigella Epidemiology
No animal reservoirs (yet identified) The Four “Fs” – food, flies, feces, fomites! Infectious dose: __ to ____ organisms! 17K to 30K cases per yr. in U.S. Risk Factors: Kids 1-4 yrs old Poor sanitation and crowding Prisons; mental institutions; long-term care facilities; extended military ops, etc. Treatment – _______ Vaccines… |
No animal reservoirs (yet identified)
The Four “Fs” – food, flies, feces, fomites! Infectious dose: 10 to 100 organisms! 17K to 30K cases per yr. in U.S. Risk Factors: Kids 1-4 yrs old Poor sanitation and crowding Prisons; mental institutions; long-term care facilities; extended military ops, etc. Treatment – typically none (self-limiting) Vaccines… |
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Salmonella - Overview
Only one species (S. _______)! …but, includes: S. typhi; S. typhimurium; S. choleraesuis; S. paratyphi A/B; S. enteriditis Sub-spp. based on _,_ and _ serotypes ___ groups based on disease category Typhoidal – S. _____, S. ______ Human is primary host; human fecal-oral Non-typhoidal – all the others Reptiles, birds, mammals (including humans) Animal fecal-human oral |
Only one species (S. enterica)!
…but, includes: S. typhi; S. typhimurium; S. choleraesuis; S. paratyphi A/B; S. enteriditis Sub-spp. based on O, H and K serotypes Two groups based on disease category Typhoidal – S. typhi, S. paratyphi Human is primary host; human fecal-oral Non-typhoidal – all the others Reptiles, birds, mammals (including humans) Animal fecal-human oral |
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Salmonella Diseases
______ fever Inc. period: 7 to 20 days; then wks. duration (8+) Early constipation; then ____________ (late) < __ hrs. ; < 7 days and/or recrudescence __________ – compromised CMI Inc. period variable; variable duration No __ symptoms May include “metastatic” infection Enterocolitis* Inc. period: 1 to 2 days; 2 to 5 day duration Vomiting; diarrhea |
Enteric fever
Inc. period: 7 to 20 days; then wks. duration (8+) Early constipation; then bloody diarrhea (late) < 48 hrs. ; < 7 days and/or recrudescence Septicemia – compromised CMI Inc. period variable; variable duration No GI symptoms May include “metastatic” infection Enterocolitis Inc. period: 1 to 2 days; 2 to 5 day duration Vomiting; diarrhea |
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Salmonella Diseases produces these 3 symptoms
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Enterocolitis
Enteric fever Septicemia |
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Salmonella Virulence Factors
Encoded on pathogenicity islands Virulence “effectors” and secretion accessory proteins - which pathway? ____ involved Large cryptic plasmid in S. ____ Required for virulence; gene functions unknown DNA homology w large plasmid of __________. Yikes! Vi capsule: N-actyl galactosaminuronic acid Inhibits _______-mediated lysis and chemotaxis Antibodies against capsule protective |
Encoded on pathogenicity islands
Virulence “effectors” and secretion accessory proteins - secretion III TTSS involved Large cryptic plasmid in S. typhi Required for virulence; gene functions unknown DNA homology w large plasmid of Yersinia pestis. Yikes! Vi capsule: N-actyl galactosaminuronic acid Inhibits complement-mediated lysis and chemotaxis Antibodies against capsule protective |
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Salmonella Epidemiology
S. typhi: infectious dose = 10^_ (low end) _______ sole reservoir many asymptomatic carriers Persists in ____ _______ Major cause of M&M in developing countries 30M cases per yr; 500,000 deaths 500 cases / yr in U.S. Non-typhoidal ______ primary source 50,000 cases/yr in U.S. |
S. typhi: infectious dose = 10 3 (low end)
humans sole reservoir many asymptomatic carriers Persists in gall bladder Major cause of M&M in developing countries 30M cases per yr; 500,000 deaths 500 cases / yr in U.S. Non-typhoidal Poultry and poultry products primary source 50,000 cases/yr in U.S. |
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Treatment of Salmonellosis
Enterocolitis fluid and electrolyte replacement _______ not required Typhoid fever ____________ or __________ Decreases mortality rate from 15% down to 1% _______ and ____________ Licensed vaccine available for Typhoid Ty21a, live-attenuated, oral Animal vaccines for non-typhoidal strains |
Enterocolitis
fluid and electrolyte replacement antibiotics not required Typhoid fever Chloroamphenicol or ampicillin Decreases mortality rate from 15% down to 1% Cephalosporins and fluoroquinolones Licensed vaccine available for Typhoid Ty21a, live-attenuated, oral Animal vaccines for non-typhoidal strains |
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Yersinia spp.
Three species pathogenic in mammals… Y. pestis NOT a GI pathogen; clonal to Y. pseudotuberculosis Y. enterocolitica Y. pseudotuberculosis Disease in humans via feces-contaminated food and/or water Facultative ________; optimal growth at room temperature; motile at room temp. |
Three species pathogenic in mammals…
Y. pestis NOT a GI pathogen; clonal to Y. pseudotuberculosis Y. enterocolitica Y. pseudotuberculosis Disease in humans via feces-contaminated food and/or water Facultative anaerobes; optimal growth at room temperature; motile at room temp. |
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Which Yersinia spp is not a GI pathogen?
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Y. pestis
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Three Yersinia species pathogenic in mammals…
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Y. pestis
NOT a GI pathogen; clonal to Y. pseudotuberculosis Y. enterocolitica Y. pseudotuberculosis |
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Diseases of the Enteropathogenic Yersiniae
Enterocolitis Mainly caused by Y. ___________ Fever; diarrhea; blood and white cells in stool Reiter’s Syndrome (aseptic polyarthritis) Can occur weeks to months after diarrhea Septicemia: rare Mesenteric adenitis Mimics _______: fever; lower right quadrant pain; enlarged lymph nodes Y. ________ OR Y. _________. |
Enterocolitis
Mainly caused by Y. enterocolitica Fever; diarrhea; blood and white cells in stool Reiter’s Syndrome (aseptic polyarthritis) Can occur weeks to months after diarrhea Septicemia: rare Mesenteric adenitis Mimics appendicitis: fever; lower right quadrant pain; enlarged lymph nodes Y. pseudotuberculosis OR Y. enterocolitica |
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Yersinia Pathogenesis
Is it invasive? Intestinal __ cells initial target Can replicate within and destroy ______ Lymphotropic Can penetrate ileal mucosa to lymph nodes Numerous virulence determinants Chromosomal and plasmid-mediated |
Invasive on epithelial cells
Intestinal M cells initial target Can replicate within and destroy macrophages Lymphotropic Can penetrate ileal mucosa to lymph nodes Numerous virulence determinants Chromosomal and plasmid-mediated |
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Is Yersinia lymphotropic
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Yes
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Yersinia Virulence Factors
Which two Chromosomal genes are required for invasion? Plasmid-encoded (75 kb pLcr) "_____________ ______ ___________” (LCR) genes Expression up-regulated by ____ temp and ____ Ca++ Gene products… |
Chromosomal
Inv Ail Plasmid-encoded (75 kb pLcr) “Low calcium response” (LCR) genes Expression up-regulated by high temp and low Ca++ Gene products… |
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Virulence Factors –cont.
“_________ _______ __________” (YOPs) Two classes: ______ and _________ Effectors – enzymatic activity YopE YopH YopJ YopM YopN YpkA YadA (YopA) LcrV |
Virulence Factors –cont.
“Yersinia Outer Proteins” (YOPs) Two classes: effectors and translocators Effectors – enzymatic activity YopE YopH YopJ YopM YopN YpkA YadA (YopA) LcrV |
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Virulence Factors –cont.
Translocators – part of a _____; numerous components Syc’s: Yop ______ chaparones YopB and YopD - “_____ complex” YscC YscF Others LcrV = __ antigen Also encoded on the Lcr plasmid (pLcr) Mutants of lcrV are ________ Required for _______ of Yop effectors into target cells Binds TLR-2 and CD-14 IL-10 Binds TLR-4 apoptotic cascade |
Translocators – part of a TTSS; numerous components
Syc’s: Yop effector chaparones YopB and YopD - “docking complex” YscC YscF Others LcrV = V antigen Also encoded on the Lcr plasmid (pLcr) Mutants of lcrV are avirulent Required for translocation of Yop effectors into target cells Binds TLR-2 and CD-14 IL-10 Binds TLR-4 apoptotic cascade |
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Epidemiology and Treatment
Y. enterocolitica ______ in Europe Y. pseudotuberculosis Certain serotypes associated w disease 3 of __ Y. enterocolitica 1 of _ Y. pseudotuberculosis Distinct geographic distribution Infections usually self-limiting Septicemia treated w amino_______ Experimental oral vaccines |
Y. enterocolitica endemic in Europe
Y. pseudotuberculosis Certain serotypes associated w disease 3 of 50 Y. enterocolitica 1 of 6 Y. pseudotuberculosis Distinct geographic distribution Infections usually self-limiting Septicemia treated w aminoglycosides Experimental oral vaccines |
