Lecture 6 - Enterics Flashcards
What are enterics?
Facultative Gram negative, rod-shaped bacteria common to or occurring as pathogens in the intestinal tract
Other name for enterics?
Enteric bacilli
Gaseous requirement of enterics?
Facultative anaerobe
What are 12 medically important (esp. in nosocomial infections) genera of the family enterobacteriaceae?
- Escherichia
- Salmonella
- Shigella
- Yersinia
- Proteus
- Providencia
- Morganella
- Citrobacter
- Enterobacter
- Pantoea
- Serratia
- Klebsiella
What body sites can enterobacteriaceae infect?
ANY
What are some infections that enterobacteriaceae cause?
- Common community acquired infections:
- Enteritis/colitis
- Cystitis/pyelonephritis - Nocosomial infections (all categories)
What body site does Escherichia infect?
CNS
What body site does Salmonella infect?
GIT
What body site does Shigella infect?
GIT
What 2 enterobacteriaceae infect the CNS?
- Escherichia
2. Citrobacter
What 3 enterobacteriaceae infect the lower respiratory tract?
- Klebsiella
- Enterobacter
- Escherichia
What 3 enterobacteriaceae infect the bloodstream?
- Klebsiella
- Enterobacter
- Escherichia
What 4 enterobacteriaceae infect the GIT?
- Salmonella
- Shigella
- Escherichia
- Yersinia
What 4 enterobacteriaceae infect the urinary tract?
- Escherichia
- Proteus
- Klebsiella
- Morganella
What enterobacteriaceae is responsible for 90% of UTIs acquired in community conditions?
Escherichia
What are the 2 physical features of enterobacteriaceae?
- Gram negative rods (0.5 x 2 microns)
2. Motility: when motile by peritrichous flagella (Klebsiella and Shigella are the only non-motile)
What are peritrichous flagella?
Multiple flagella emanating from all aspects of the cell periphery (in contrast to polar flagella localized to one end of the cell)
What are the 3 biochemical/metabolic features of enterobacteriaceae?
- Facultative anaerobes
- Ferment glucose
- Oxidase negative
What is an oxidase test?
Test that distinguishes Enterobacteriaceae from other important enteric pathogens, Vibrios and Campylobacter, which are oxidase positive
What are the media for selective isolation and differentiation of enterobacteriaceae?
Many of them (do not need to know names) that use bile salts or dyes that inhibit other organisms (typically gram + bacteria) and contains a differentiating compound that some species can use and others cannot (e.g. lactose)
What is the difference between Lac positive and Lac negative enterobacteriaceae?
- Lac positive: cells that can ferment lactose
2. Lac negative: cells that cannot ferment lactose
What are 4 prominent Lac negative enterics?
- Salmonella
- Shigella
- Yersinia
- Proteus
What are fecal coliforms?
Lac positive enterics, primarily E. coli indicative of fecal contamination
What is speciation of enterobacteriaceae based on?
Based on metabolic/biochemical reactions during which enterobacteriaceae react with different compounds to produce different color compounds, gases, etc.
Purpose of API strips?
Speciation of enterobacteriaceae
What test is done once an enterobacteriaceae is speciated?
Subtyping based on serotyping with the:
- O-antigen: LPS
- H-antigen: flagellum
- K-antigen: capsule
What is the K-antigen called in Salmonella?
Vi-antigen
What is the most abundant facultative anaeroble in the gut?
E. coli
What vitamin does E. coli produce?
Vitamin K2
What are disease associated subtypes of E. coli? Other name for them?
Subtypes of E. coli that have acquired virulence genes through horizontal gene transfer
= pathovars
Important E. coli pathovars to know?
- Uropathogenic
- Neonatal meningitis
- Large collection that produces GIT diseases
What is the clinical significance of E. coli pathovars?
- Pathovars have distinct pathogenic mechanisms and, consequently, can have variable clinical presentations
- Future physicians will be treating, and should be alert to the appearance of, new and/or atypical enteric infections
What is the most common E. coli pathovar? What does it cause?
Enterohemorrhagic E. coli causing hemorrhagic colitis
3 symptoms of hemorrhagic colitis?
- Watery, progressing to grossly bloody diarrhea (after 3 days)
- Abdominal cramping
- Fever rare/low grade
What is life-threatening sequela of hemorrhagic colitis? How often does this happen?
HUS = hemolytic uremic syndrome, resulting in kidney failure and death
Happens in 15% of children below 10 yo with enterohemorrhagic E. coli infection
Incubation period of enterohemorrhagic E. coli infection?
3 days
Which patients are most at risk for HUS?
Children and the elderly
Where in the world are enterohemorrhagic E. coli infections more common? Why?
Developed nations
Due to ways cattle is raised
What subtype of enterohemorrhagic E. coli infection is the most common?
O157:H7
Reservoir of enterohemorrhagic E. coli?
Cattle and other ruminants
Does enterohemorrhagic E. coli cause disease in animals?
NOPE
Transmission route of enterohemorrhagic E. coli infections?
Fecal-oral
Transmission vehicles of enterohemorrhagic E. coli infections?
- Ground beef
- Spinach
- Unpasteurized milk
- Lettuce
- Apple cider
- Radish sprouts
- Water: municipal, swimming
- Animal contact: farms, petting zoos
- Person to person (rare)
Infectious dose of enterohemorrhagic E. coli?
10-100 bacteria (low)
What determines the infectious dose of a particular bacteria?
Stomach acid provides a strong barrier to intestinal infection so acid resistant intestinal pathogens have lower infectious doses and reduced stomach acidity increases susceptibility to infection
Describe the pathogenesis of hemorrhagic colitis.
- Bacteria directly subvert columnar epithelial cells by injecting effector proteins through a syringe-like assembly known as a type III secretion system => causing attaching and effacing (A and E) lesions => reduced absorptive surface and tight junction disruption => diarrhea
- Bacteria produce the shiga toxin (Stx) encoded by bacteriophage: AB toxin that binds the Gb3 receptor and deadenylates 60S rRNA (with N-glycosidase) => shuts down protein synthesis => cell and organ damage (primarily endothelial cells due to Gb3 expression) => bloody diarrhea, renal failure, and CNS manifestations
Other name for shiga toxin produced by enterohemorrhagic E. coli? Where does the name come from?
Verotoxin
Resembles a toxin produced by Shigella bacteria, but in Shigella the toxin is part of the genome so treating with antibiotics does not have the risk of amplification
2 types of shiga toxins? Which is more potent? What to note?
Stx 1 and 2***
NOTE: bacteria produce either or both
What are shiga toxins encoded by?
λ phage in EHEC, temperate phage that lysogenize until they receive a particular signal
3 clinical features of HUS?
- Microangiopathic hemolytic anemia
- Thrombocytopenia
- Glomerular thrombotic microangiopathy
Treatments for enterohemorrhagic E. coli infections?
- Self-resolving 5-8 days
- Supportive therapy, particularly for HUS
- Antibiotic use controversial because it can make the situation worse due to the release of greater levels of toxins
- Experimental strategies: Gb3 receptor analogs and immunization against Stx
3 microbiological features of the genus Shigella?
- Oxidase negative
- Lactose negative
- Nonmotile
How do Shigella and E. coli relate to each other?
Shigella is a pathovar of E. coli
What are 4 Shigella species?
- S. dysenteriae
- S. flexneri
- S. boydii
- S. sonnei
What disease do Shigella infections cause? 2 names
Shigellosis = (bacillary) dysentery
4 clinical symptoms of shigellosis? What to note?
- Initial watery diarrhea
- Subsequent abdominal cramping
- Fever
- Bloody, mucoid discharge with prominent fecal leukocytes
NOTE: symptoms can be mild to severe depending on species: sonnei < flexneri < dysenteriae
Fatality rate of shigellosis due to S. dysenteriae? What causes death?
5-15%
Due to hemorrhaging and ulceration of the colon
Definition of dysentery?
Triad of symptoms:
- Abdominal cramps
- Tenesmus
- Frequent, small-volume bloody, mucoid discharge
What is the significance of fecal leukocytes?
Invasive enteric pathogens, like Shigella, Salmonella, Yersinia, and Campylobacter, provoke a inflammatory response resulting in high fecal leukocyte count
Primary reservoir of Shigella?
Humans
Infectious dose of Shigella infections?
< 200 bacteria (low)
What species are most Shigella infections in the US due to?
S. sonnei
What populations are most at risk of Shigella infections?
- Children < 15 yo due to outbreaks in daycares and institutional settings
- Traverler’s diarrhea
What are secondary attacks? What infections have a high rate of these?
High chance of additional cases after one focus case in a household
Shigella infections
Are Shigella infections more common in the US or the rest of the world?
Rest of the world: 15,000 vs 150 million cases/year
What species are most Shigella infections in the world due to?
S. flexneri
Describe the pathogenesis of Shigella infections.
Bacteria is phagocytosed by microfold cells of the GIT lumen and transcytosed to the basal aspect of the cells and are either phagocytosed by activated macrophages or interact with the basal surface to induce their own phagocytosis by the epithelial cells => they replicate in the epithelial cells => use the actin cytoskeleton of the cell to push themselves from one cell to the next => intracellular infection spreads throughout the epithelial layer of the colon => epithelial cells eventually killed => bloody, mucoid discharge
Which only Shigella species produces a toxin? What is it? Effects?
S. dysenteriae Type I produces shiga toxin => bloody diarrhea and renal failure
Treatment for Shigella infections?
Antibiotics
Transmission vehicles of Salmonella infections? Most common?
- Tomatoes
- Jalapenos
- Cilantro
- Papaya juice
- Chicken eggs and poultry***
- Peppers
- Peanuts
- Cereal
- Water
Why are there so many transmission vehicles of Salmonella?
Because they are universally present in the environment: human and animal GITs, water, soil, etc.
4 microbiological features of the Salmonella genus?
- Oxidase negative
- Lactose negative (99%)
- Motile (phase variable)
- H2S producer (hydrogen sulfide)
What are the 2 taxonomic nomenclatures for the genus Salmonella?
- Traditional: based on O and H antigens => ~2,500 species organized into serogroups A to I = Kauffman-White scheme
- Current: 2 species => S. enterica (with 6 subspecies) and S. bongori
Host range and diseases of Salmonella infections?
Depends on Salmonella serotype:
- Some have a broad host range, e.g. S. Typhimurium, S. Enteritidis, infect diverse animal species, and typically cause gastroenteritis in humans
- Some have a narrow host range, are specifically adapted to a preferred host and rarely manifest as gastroenteritis (e.g. S. choleraesuis in pigs and S. Typhi and Paratypihi ONLY in humans)
Disease caused by S. Typhi and Paratypihi? Which causes more severe cases?
Typhoid fever
S. Typhi causes more severe cases
What is salmonellosis? Transmission? Clinical manifestation?
Infection with a member of the genus Salmonella typically transmitted through fecal contaminated food or water
Clinical manifestations vary with serotype
2 possible clinical manifestations of non-typhoid salmonellosis?
- Gastroenteritis: watery diarrhea often with fever, nausea and vomiting
- Bacteremia
Incubation period and duration of gastroenteritis due to salmonellosis?
6-48 h incubation period
2-7 day duration and self-resolving
What % of patients with non-typhoidal salmonellosis have bacteremia?
8%
What patients are at high risk of having bacteremia due to non-typhoidal salmonellosis? What is this called?
AIDS patients at high risk (recurrent bacteremia AIDS defining)
Incidence of non-typhoidal salmonella serotypes in the US? What to note?
~40-50K cases/year
Actual: 1-1.5 M, but most cases do not get reported AND seasonal pattern with most cases in late summer/early fall
Populations at higher risk of non-typhoidal Salmonella infections?
- Children < 5 yo
2. Elderly
7 clinical symptoms of typhoid strains of Salmonell infections?
Enteric (typhoid) fever: severe systemic illness that spreads through the bloodstream
- Protracted fever for 3-4 wks
- Insidious onset
- Headache
- Anorexia
- Myalgia 10-14 days post-exposure
- GIT symptoms 1 week later
- “Rose spots” = maculopapular rash on trunk
Transmission of typhoid strains of Salmonella?
- Person to person with some individuals being asymptomatic chronic carriers (gallbladder is infected) that pass the bacteria in their feces for over a year and transmit it in areas where there is not proper sanitation (1-4% of untreated patients) => low infectious dose
- Food and water
Mortality rate of typhoid fever? What causes death?
10-15% mortality in untreated cases due to ileal perforation & hemorrhaging
Incidence of typhoid salmonella infections in the US? What to note?
400-500 cases/year
NOTE: traveler’s disease in 75% of cases
Incidence of typhoid salmonella infections in the world? What to note?
26 M cases/year
NOTE: mostly in South Asia, 80% due to S. Typhi and 200-600K deaths/year
Reservoir of typhoid Salmonella?
Humans
Describe the pathogenesis of Salmonella gastroenteritis.
Bacteria transgresses GIT epithelial layer through the microfold cells => inflammatory response with macrophages and PMNs secreting leukocytes => inflammatory diarrhea
Describe the pathogenesis of Typhoid fever.
Bacteria transgresses GIT epithelial layer through the microfold cells => inflammatory response with macrophages => bacteria survives the macrophages and grows in them, so macrophages serve as a vehicle for dissemination through the mesenteric lymph nodes => blood => liver and spleen => gallbladder => back to GIT
Why does the fever in typhoid fever take 10-14 days to appear?
Doesn’t appear until the macrophages start to lyse and release the bacteria in the bloodstream => bacteremia
Why is the genus campylobacter important?
Causes almost as many infections as Salmonella
8 microbiological features of the genus Campylobacter?
- Gram negative
- Curved/helical rod
- Single polar flagellum
- Microaerophilic (5-10% O2)
- Oxidative metabolism (do not utilize carbohydrates)
- Optimal growth at 42 C (some species)
- Oxidase positive
- Polysaccharide capsule
4 primary species of clinical importance in the genus Campylobacter? Most important one?
- C. jejuni***
- C. coli
- C. upsaliensis
- C. fetus
Why was the genus Campylobacter not recognized for a while?
- Because it only needs 5-10% O2 and need 42 degrees so wouldn’t survive under typical culture conditions
- Very small and can pass through a sterilization filter
Where are Campylobacters found?
GIT of animals and birds
Transmission vehicles of Campylobacter? Most common?
- Undercooked poultry*** (50-70% of sporadic cases)
- Raw milk
- Surface waters
- Beef
- Clams
- Cheese
- Direct contact with infected animals and pets
US incidence of Campylobacter infections? What to note?
> 2 million/yr (not reportable)
NOTE: seasonal, summer to early fall and higher in rural communities
In what population is a Campylobacter infection symptomatic?
Symptomatic infection in children and asymptomatic in adults
Pathogenesis of Campylobacter infection? What is it similar to?
Invasive organism that provokes a strong inflammatory response
Similar to Salmonella infection
Sequella of Campylobacter infection? How does this work?
Guillain-Barre syndrome = flaccid peripheral neuropathy due to inflammatory demyelination
Campylobacter sialic acid containing LOS (lipooligosaccharide: similar to LPS, but lacking outer O antigen repeats) induce cross-reactive antibodies to GM1, GM2, GD1a = “molecular mimicry”
How often does a Campylobacter infection develop into GBS?
Approx. 1 in 2000 C. jejuni infections and 30-66% of GBS cases have antecedent C. jejuni infection
3 most common infections in US?
- Salmonella
- Campylobacter
- Shigella
