Bacterial Infections of the GI Tract III Flashcards by Christopher Hauglid

Vibrio spp. (Disease-Causing spp.)

1) Vibrio cholerae (Gastroenteritsi, Bacteremia)
2) Vibrio parahaemolyticus (Gastroenteritis, Bacteremia, Wound infection)
3) Vibrio vulnificus (Bacteremia, Wound infection)

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Virbio spp. (Characteristics)

Gram negative, facultative anaerobes
COMMMA (curved) shaped
Free-living in water
Broad temperature range of growth
REQUIRE SODIUM CHLORIDE for growth
Grow at a WIDE RANGE of pH (susceptive to stomach acid, high infectious dose ~10^9)

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Vibrio cholerae (Small Intestine) (Disease)

Cholera

Asymptomatic –> severe WATERY diarrhea
2-3 day incubation
Up to 7 day duration
5 to 25% of infected individuals develop SEVERE WATERY diarrhea (abrupt onset, ~17 liters/4.5 gallons in a 150 lb person, Rice water stool, can kill within HOURS via dehydration)

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Vibrio cholerae (Small Intestine) (Epidemiology)

Spread through CONTAMINATED WATER
Infection = LONG-TERM IMMUNITY (appears to be O antigen specific)
Associated with epidemics and pandemics

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Vibrio cholerae (Small Intestine) (Typing and Epidemiology)

1) Based on O-antigens (O1 to O200+)
2) O1 = cholera toxin-producing
- Epidemic and Pandemic cholera caused by O1 serotype
a) Pandemics 1-6 caused by classic biotype
b) Current pandemic (#7) caused by El Tor biotype
- Less severe disease (1 symptomatic to 30-100 asymptomatic)
- Duration of carriage longer than classic strain
- Survives better in the environment (carried longer, shed longer)

O-antigens change = Patients no longer immune

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Vibrio cholerae (Small Intestine) (Virulence Factors (2 of them) and Pathogenesis)

1) Toxin co-regulated pilus (TCP)
- Mediated adherence to intestinal epithelial cells
* Binds to cell*

2) Cholera Toxin
- AB toxin
- Activation of adenylate cyclase –> INCREASE cAMP –> massive efflux of watery secretions
- NO significant cell damage done by toxin
- Very similar effect to ETEC LT toxin (structure and function)
- Encoded on CTXo (PROPHAGE/BACTERIOPHAGE)

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Vibrio cholerae (Small Intestine) (Diagnosis and Treatment)

Diagnosis:
-Culture (differential media; in places where cholera is not common)

Treatment:

Rehydration therapy - IV and oral
Without rehydration therapy, mortality can be as high as 90%

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Vibrio parahaemolyitcus (Small Intestine) (Disease and Virulence)

Disease:
-Explosive watery diarrhea, nausea, vomiting, abd cramps, low grade fever

Virulence:

KANAGAWA HEMOLYSIN* (VIRULENCE FACTOR)
Induces chloride secretion, thus watery diarrhea

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Vibrio parahaemolyitcus (Small Intestine) (Epidemiology and Treatment/Prevention)

Epidemiology:

Associated with consumption of RAW SHELLFISH
Most common cause of:
1) Bacterial gastroenteritis in Japan and Southeast Asia
2) Seafood associated gastroenteritis in the US

Treatment and Prevention:

Self-limiting
Proper cooking of shellfish

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Yersinia enterocolitica (Small Intestine) (Characteristics)

Gram negative coccobacilli

- Related to Yersinia pestis (Causative agent of Bubonic Plague)

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Yersinia enterocolitica (Small Intestine) (Epidemiology)

Widespread in NATURE and ANIMALS

Most isolates are AVIRULENT
Spread by ingestion of CONTAMINATED WATER, FOOD (e.g. improperly cooked PORK)

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Yersinia enterocolitica (Small Intestine) (Symptoms)

Fever, abd cramps, watery –> bloody diarrhea

-Last 1-2 weeks

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Yersinia enterocolitica (Small Intestine) (Pathogenesis)

Poorly understood
Binds to and invades M-cells in the terminal ILEUM (similar to Salmonella spp. , but via separate mechanism)
Involves T3SS and injection of Yops (Yersinia outer proteins)
Produces HEAT-STABLE ENTEROTOXIN (main reason symptoms manifest as diarrhea)

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Yersinia enterocolitica (Small Intestine) (Diagnosis and Treatment)

Diagnosis
-Stool culture

Treatment:
-Self-limiting

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Clostridium difficile (Large Intestine) (Characteristics)

Gram positive anaerobe
Non-invasive
SPORE FORMING
Emerging pathogen (Nosocomial, HAI)

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Clostridium difficile (Large Intestine) (Disease and Symptoms [Vary])

Asymptomatic carriage –> CDAD (C. diff Associated Diarrhea) –> Pseudomembrane colitis –> fulminant colitis with TOXIC MEGACOLON

Forms large plaques on top of intestinal epithelium, reducing uptake of water

Clostridium difficile (Large Intestine) (Pathogenesis)

Toxin A and Toxin B

-Caused DAMAGE to the MUCOSA by disrupting the host cell CYTOSKELETON and causing diarrhea

Clostridium difficile (Large Intestine) (Diagnosis, Treatment, and Prevention)

Diagnosis:

Toxin detection in the stool
Culture is NOT HELPFUL (as C diff is part of normal microbiota in 5-10% of population)

Treatment:
-Oral Vancomycin or Metronidazole

Prevention:
-Fecal Transplant

Clostridium difficile (Large Intestine) (Epidemiology and Risk Factors)

Mainly seen in patients in the HOSPITAL for a SURGICAL PROCEDURE or being treated with BROAD SPECTRUM ANTIBIOTICS that alter normal microbiota

EHEC (Large Intestine) (Characteristics)

Gram negative, facultative anaerobe
O157:H7 (a lot of news coverage)
Animal reservoirs** = *Cattle or other ruminants (Animals are ASYMPTOMATIC; will not know they have it unless cultured)
Generally non-invasive

Mnemonic: EHEC –> “H” = Hamburger

EHEC (Large Intestine) (Epidemiology)

Sporadic cases and outbreaks mainly in the developed world

-Associated with contaminated ground beef (HAMBURGER) and vegetables (washed with water from rivers/streams)

EHEC (Large Intestine) (Disease)

HEMORRHAGIC COLITIS = blood diarrhea (MARKED blood)
No fever, marked abdominal tenderness
Sequelae –> HEMOLYTIC UREMIC SYNDROME (HUS) = Anemia and kidney failure

EHEC (Large Intestine) (Pathogenesis)

Attaching and Effacing lesions like PEEC (***Uses TYPE III system to inject protein in)
Shiga-like toxin (Verotoxin)
–> Blocks translation by cleaving part of the 60S subunit of the ribosome

EHEC (Large Intestine) (MOA)

E. coli O157:H7 binds to brush border of intestinal mucosa
E. coli O157:H7 produces VEROTOXIN that destroys microvilli
Verotoxin (i.e. Shiga-like Toxin [Stx]) enters blood, causing vascular endothelial damage and increased platelet aggregation
Platelet-Fibrin thrombi form causing ischemic damage to colon, kidneys, and other tissues
- Hemorrhagic Colitis
- Hemolytic Uremic Syndrome (HUS)

What causes kidney damage in EHEC patients?

Glomeruli are rich in toxin glycolipid receptor ***Gb3***, which binds to Shiga-like toxin (Verotoxin), causing thrombi to form and cause ischemic damage to the kidney

EHEC (Large Intestine) (Diagnosis)

* **Presumptive --> bloody diarrhea WITHOUT fever*** - Culture - PCR (NAAT): Detection of stx gene that encodes toxin - Rapid diagnostic test kits

EHEC (Large Intestine) (Treatment)

- Supportive therapy - Antibiotic therapy not beneficial and may be harmful a) Antibiotic use --> bacterial cell damage --> lysogenic phage (Stx) --> lytic cycle --> increased toxin production --> ***increase in HUS rate*** * **Antibiotic therapy is contraindicated***

EHEC (Large Intestine) (Prevention)

-Properly cook hamburger, raw vegetables

Shigella spp (Large Intestine) (Characteristics)

Gram negative rods, facultative anaerobe Intracellular pathogens ***Dysentery***

Shigella spp (Large Intestine) (Epidemiology)

~150 million cases, 600,000 deaths per year worldwide - Humans are the ONLY RESERVOIR - Transmission through FECAL-ORAL ROUTE - Extremely low infectious dose, < 10 organisms - Incidence directly related to hygiene (poor sanitary infrastructure, crowded healthcare systems; DAY CARE CENTERS)

Shigella spp (Large Intestine) (Global Species Distribution)

1) S. soneii: DevelopED countries 2) S. flexneri: DevelopING countries 3) S. dysentariae: underdeveloped tropical areas (most severe infections due to HIGH SHIGA TOXIN production)

Shigella spp (Large Intestine) (Clinical Manifestations of Shigellosis)

- 1 to 3 days post-ingestion - Disease usually self-limiting, 2 to 5 days post-manifestation - Generally strain-specific a) S. sonneii: - -Fever, malaise, and watery diarrhea b) S. flexerni and S. dysenteriae: - -Dysentery: fever, malaise, watery diarrhea, abdominal cramps, tenesmus (frequently feeling the need to defecate), frequent ***bloody and pus-filled*** stools - -S. dysenteriae- potential for HEMOLYTIC UREMIC SYNDROME (HUS) * **HIGHLY INFLAMMATORY DISEASE***

Shigella spp (Large Intestine) (Pathogenesis Part I)

- Acid resistant*** - Adhere selectively to and pass through M-cells (Similar to Salmonella***) - Phagocytosis by macrophages - Rapid escape from phagosome (Unknown mechanism) - Rapid in induction of macrophage apoptosis * **Leads to a lot of inflammation and pus production***

Shigella spp (Large Intestine) (Pathogenesis Part II)

- Interact with basolateral face of ***enterocytes*** - Induce uptake via T3SS (***injection of Ipa proteins; cytoskeletal rearrangement***) - Lysis of endocytic vacuole (unknown mechanism) - Spread to neighboring cells via actin polymerization at a pole (hijacking of host actin; evasion of host defenses) ***Can jump between cells like Listeria***

Shigella spp (Large Intestine) (Pathogenesis Part III)

- Enterocytes escape/invasion leads to cell death - Ulcers*** form in infected areas - Diarrhea primarily from severe inflammation - ***Shiga toxin production (Stx)*** 1) Binds host Gb3 receptor 2) Inhibits translation = cell death = tissue damage 3) Glomerular endothelial cells rich in Gb3 (Hemolytic Uremic Syndrome HUS)

Shigella spp (Large Intestine) (Diagnosis)

Stool culture | Serological tests to confirm species

Shigella spp (Large Intestine) (Treatment and Prevention)

Treatment: - Rehydration therapy - Antibiotic treatment (shorten duration of illness and/or limit disease severity; Ampicillin resistance is common; Ampicillin choice dependent on susceptibility profile) Prevention; - No vaccine - Improved sanitation and personal hygiene * **Infection does not confer immunity*** (Can get it over and over again)

Enteroinvasive E. coli (Large Intestine)

- Very uncommon - Same as Shigella infection EXCEPT NO SHIGA TOXIN - Appears E. coli obtained pathogenicity island from Shigella spp. via horizontal gene transfer ***Certain sexual acts associated with increased risk: oral to anal contact (transmission of Salmonella spp. Campylobacter jejuni, and Shigella spp.)