L33-35: Bacterial Infections of the GI Tract Flashcards
Diarrhea
Passage of 3+ loose/liquid stools per day, usually result in disease of small intestine
What are the host defenses that the GI tract can use to prevent disease?
Continuous epithelium, mucus (but sometimes triggers virulence), low pH, gut motility, shedding of epithelium, bile, secretory IgA, normal microbiota
Gastritis
Inflammation of the stomach
Gastroenteritis
Inflammation of stomach and intestines, characterized by nausea, vomiting, diarrhea, and abdominal discomfort/pain
Dysentery
Inflammatory disorder of the GI tract often causing diarrhea with blood/pus, pain, fever, abdominal cramps – normally associated with large intestine
Enteritis
Inflammation of the intestines, especially small intestine
Enterocolitis
Inflammation of the mucosa of small and large intestine
Colitis
Inflammation of the large intestine, specifically the colon
Inflammatory bacteria characteristics
Cause damage to the intestine through inflammation, more likely to see fecal occult/leukocytes or visible blood
Inflammatory bacteria types
Salmonella spp., Campylobacter jejuni, C. diff (severe cases), EHEC, EIEC, Shigella spp., Vibrio parahaemolyticus, Yersinia enterocolitica
Non-inflammatory bacteria characteristics
Pass through the intestine or adhere to intestinal epithelium – either don’t produce toxins or non-cytotoxic toxin
Non-inflammatory bacteria types
EPEC, ETEC, Vibrio cholerae, Listeria monocytogenes
Which bacteria cause bloody diarrhea? (sometimes or often)
EHEC, Campylobacter jejuni, Shigella spp., Yersinia enterocolitica, EIEC, C. diff, Vibrio parahaemolyticus
Which bacteria cause watery diarrhea? (rarely blood)
EPEC, ETEC, food poisoning, Clostridium perfringens, Bacillus cereus, Vibrio cholerae, Salmonella spp., Listeria monocytogenes
Which bacteria cause symptoms 1-8 hrs after ingestion and what is their mechanism?
Preformed toxin – S. aureus, Bacillus cereus (emetic), C. botulinum
Which bacteria cause symptoms 8-16 hrs after ingestion and what is their mechanism?
Production of toxin after ingestion – B. cereus (diarrheal), C. perfringens, C. botulinum
Which bacteria cause symptoms 16+ hrs after ingestion and what is their mechanism?
Adherence, growth and virulence factor production – Shigella, Salmonella, Listeria monocytogenes, all E. coli species, Campylobacter, Vibrio species
2 types of bacterial food poisoning
- Toxins produced before food is eaten
2. Large number of spores that germinate in intestine and produce toxins
Symptoms of bacterial food poisoning
Diarrhea, vomiting, but NO FEVER
4 main causes of bacterial food poisoning
S. aureus, C. botulinum, C. perfringens, Bacillus cereus
S. aureus in food poisoning
Preformed toxin, causes severe vomiting, diarrhea, and abdominal pain in 1-8 hrs – toxin is HEAT-STABLE (not well understood) – supportive treatment
Disease process of C. botulinum
Causes botulism, mediated by botulism toxin – early stage: vomiting, diarrhea, abdominal pain 1-16 hrs later, late stage: flaccid paralysis leading to progressive muscle weakness and respiratory arrest
Mechanism of infection of C. botulinum
Ingestion of preformed toxin or large number of spores
How does the botulism toxin work?
Acts at neuromuscular junction and interferes with signaling at synapses – if patient survives there can be lingering weakness and dyspnea up to a year later
How do adults and infants get infected with C. botulinum?
Adults: improperly canned food items
Infants: honey
Infant botulism (floppy baby syndrome)
Occurs between birth-6 months; germination of C. botulinum spores in intestines leads to toxin production (due to permeability of intestinal mucosa)
Treatment for botulism
Supportive or IV anti-toxin administration if severe
Clostridium perfringens characteristics
Gram+ rod that forms spores
C. perfringens disease process
Mediated by C. perfringens enterotoxin, associated with meat/gravies held below standard temp and begins 8-16 hrs after ingestion
Pathogenesis of C. perfringens
Survive cooking, grow in food, ingested and sporulate –> enterotoxin produced –> diarrhea
Treatment for C. perfringens
Supportive therapy
Bacillus cereus characteristics
Gram+ rod, spore-forming
Emetic form of Bacillus cereus
Vomiting, nausea, and abdominal cramps 1-8 hrs due to ingestion of preformed heat-stable enterotoxin – related to improper storage of rice
Diarrheal form of Bacillus cereus
Diarrhea, nausea, and abdominal cramps 8-16 hrs later, production of heat-liable enterotoxin in intestine – comes from meat, vegetables
What is the main difference between the pathogens that cause food poisoning and those that cause other disease?
The bacteria that cause food poisoning do so by release of toxin but cannot actually bind to the digestive tract
Helicobacter pylori characteristics
Gram- curved rod, microaerophilic, produce flagella and uses urease to cause disease
What disease does Helicobacter pylori cause?
Ulcers and chronic gastritis (related to stomach cancer)
Pathogenesis of Helicobacter pylori
Penetrates the stomach epithelium and produces NH3 using its urease (neutralizes acid of stomach), then exposes underlying tissue due to damage and this is where ulcers can form
Diagnosis of Helicobacter pylori
Urea breath test (or biopsy)
Treatment of Helicobacter pylori
Only treat after positive test – combination of antibiotics and proton pump inhibitor
Listeria monocytogenes characteristics
Gram+ facultative anaerobic, short rods, intracellular – can persist in the cold!!!
Epidemiology of Listeria monocytogenes
Animal reservoirs such as mammals, birds, and fish; contaminated food is primary source (ready to eat meats, cheeses), high risk of infection in pregnant women, elderly, immunocompromised – passed mother to fetus
Clinical manifestation of Listeria monocytogenes
Usually asymptomatic in adults (but fever); causes bacteremia or meningitis/encephalitis in immunocompromised adults
Listeria monocytogenes and pregnant women
May develop nausea, fever, diarrhea; should check if fever with no obvious infection – can be passed to newborn
Neonatal Listeria monocytogenes infection
Granulomatosis infantiseptica = pyogenic granulomas all over body, meningitis, encephalitis, can be early (in utero – premature or death) or late onset
Pathogenesis of Listeria monocytogenes
Adhere and induce uptake into the cell with IntA, internalized in endocytic vacuole which activates Listeriolysin O (LLO) – can spread by replicating in host cell cytosol and using ActA-mediated actin polymerization to spread
Where can Listeria monocytogenes spread?
First to neighboring cells and blood stream, then to liver, spleen, and CNS
Diagnosis of Listeria monocytogenes
Microscopy is too sensitive, best is cold enrichment selection (because it grows in the cold)
Treatment of Listeria monocytogenes
Beta-lactam or trimethoprim-sulfamethoxazole (no vaccine, cook properly)
MacConkey agar test
Tests for lactose fermentation – positive = red (E. coli, etc.), negative = white (Salmonella, Shigella, etc.)
Indole test
Tests for indole production – positive = red (E. coli, Vibrio spp, etc.), negative = no color change (Salmonella)
Hydrogen sulfite (H2S) production test
Forms a black precipitate – positive = Salmonella, negative = Shigella
4 main E. coli pathogens
ETEC = enterotoxigenic EPEC = enteropathogenic EHEC = enterohemorrhagic EIEC = enteroinvasive
EPEC characteristics
Gram-, facultative anaerobe, moderately invasive (generally non-inflammatory)
Epidemiology of EPEC
Important in infants in developing country, 5-10% of pediatric diarrhea (ePec for Pediatric)
Pathogenesis of EPEC
- -EPEC finds its way into the intestines where it interacts with cells through BfpA
- -Type III secretion system (needle injection) that injects protein Tir into cytosol and inserts into membrane to become receptor for bacteria
- -Causes AE lesion (loss of microvilli) leading to watery diarrhea
- -NO TOXINS used
Diagnosis of EPEC
Ferments lactose (red on MacConkey agar), indole positive, PCR
Treatment of EPEC
Supportive therapy
ETEC characteristics
Gram- facultative anaerobe, non-invasive, causes watery diarrhea (known as traveler’s diarrhea – eTec for Traveler)
Pathogenesis of ETEC
Attaches to the surface of the cell with its fimbriae, produces both LT (heat liable) and ST (heat stable) toxins
How does ETEC’s LT toxin work?
AB toxin that finds its way into the cell to activate adenylate cyclase (which increases cAMP) to cause solutes and water to leave the cells – watery diarrhea
How does ETEC’s ST toxin work?
Not an AB toxin – doesn’t enter cell but increases cGMP to cause watery diarrhea
Diagnosis of ETEC
Clinical history is key, DNA probes can detect LT and ST encoding genes (not common yet)
Treatment of ETEC
Supportive therapy
Salmonella Typhi characteristics
Gram- facultative anaerobe, motile rods, flagellated (H antigen), acid tolerant, intracellular – INFLAMMATORY
Epidemiology of S. Typhi
Only infects humans, fecal-oral transmission
Symptom progression of S. Typhi
Fever with headache -> rising fever over 3 days –> typhoid fever (prolonged) –> GI symptoms (also it’s shed in stool)
Pathogenesis of S. Typhi
M cells (in Peyer’s patches in the ilium) take antigens and present them, leading to tolerance – S. Typhi uses this and type III secretion to inject Ssps into cell, which induces membrane ruffling around bacteria that cause them to get enveloped
Pathogenesis of S. Typhi leading to bacteremia
Escapes enterocytes and infects macrophages in the same way –> escapes from macrophages to cause bacteremia with prolonged fever
Diagnosis of S. Typhi
Culture of stool and blood samples on selective media
Treatment of S. Typhi
Antibiotic therapy based on susceptibility profile (fluoroquinolones, trimethoprim-sulfamethoxazole or broad spectrum cephlosporin)
Prevention of S. Typhi
Avoid potential sources of infection (no water, raw fruits or vegetables), vaccination in endemic areas
Nontyphoidal Salmonella types
Serovars Cholerasuis, Enteritidis, and Typhimurium
Nontyphoidal Salmonella characteristics
Gram- facultative anaerobe, motile rods, flagellated (H antigen), acid tolerant, intracellular pathogens – SAME AS S. TYPHI
Epidemiology of nontyphoidal Salmonella
Industrialized countries, higher in young children/allergies, sources of infection are contaminated food (transmission can go between humans, food, and animals)
Clinical manifestations of nontyphoidal Salmonella
Begins between 6-48 hours post-ingestion, nausea/vomiting with cramps and watery diarrhea lasting for 3-4 days (can be with or without blood)
Pathogenesis of nontyphoidal Salmonella
Same as S. Typhi except it does not have prolonged fever component
Diagnosis of nontyphoidal Salmonella
Serology (detect anti-Vi antigen antibodies), culture from blood and stool – REMEMBER white on MacConkey (non-lactose fermenting) and H2S producing (black precipitate)
Treatment of nontyphoidal Salmonella
Supportive therapy, antibiotics not recommended except for severe (enhances carrier state) – no vaccine for prevention!!
Campylobacter jejuni characteristics
Gram- rod, curved or seagull shaped, microaerophilic (needs less O2), in many animal reservoirs – INFLAMMATORY
Disease of Campylobacter jejuni
Ulceration and acute enteritis, watery diarrhea, can lead to sepsis and GBS – not much is known about pathogenesis
Guillain-Barre syndrome (GBS) and Campylobacter jejuni
C. jejuni is not the only cause of GBS but it does cause it by mimicking something on neurons that causes the immune system to start attacking neurons – progressive muscle weakness accompanied by absent or depressed deep tendon reflexes with varied symptoms related to paralysis
Diagnosis of Campylobacter jejuni
Culture (done routinely) on selective media in microaerophilic environment
Treatment of Campylobacter jejuni
Supportive therapy, antibiotics only used for invasive disease
Vibrio spp. characteristics
Gram- facultative anaerobe, comma shaped, live in water, have wide range of growth abilities – 3 types: V. cholerae and V. parahaemolyticus (3rd type not important) – INFLAMMATORY
Disease of V. cholerae
Cholera – can be asymptomatic all the way to severe watery diarrhea (abrupt onset and can kill within hours, “rice water” stool)
Epidemiology of V. cholerae
Spread through contaminated water, important cause of diarrheal disease, infection leads to long-term immunity (O-antigen specific)
Cholera pandemics
O1 serotype causes these – classic biotypes seen in pandemics 1-6, El Tor biotype seen in current pandemic
Pathogenesis of cholera
Due to cholera toxin – AB toxin that activates adenylate cyclase to increase cAMP –> massive efflux of watery secretions but does not cause significant cell damage (similar to ETEC LT toxin)
Diagnosis of V. cholerae
Culture (in places where not common)
Treatment of V. cholerae
Rehydration therapy is very important!!! (otherwise will kill)
Disease of V. parahaemolyticus
Causes explosive watery diarrhea, nausea, vomiting, abdominal cramps, low grade fever
Virulence factor of V. parahaemolyticus
Kanagawa hemolysin – induces chloride secretion –> watery diarrhea
Epidemiology of V. parahaemolyticus
Associated with consumption of raw shellfish, common cause of bacterial gastroenteritis associated with seafood
Treatment and prevention of V. parahaemolyticus
Proper cooking of shellfish, self-limiting
Yersinia enterocolitica characteristics
Gram- coccobacilli, inflammatory
Epidemiology of Y. enterocolitica
Widespread in nature and animals, most isolates avirulent and spread by ingestion of contaminated food/water
Sypmtoms of Y. enterocolitica
Fever, abdominal cramps, watery-bloody diarrhea – lasts 1-2 weeks
Pathogenesis of Y. enterocolitica
Poorly understood, but binds to and invades M cells (like Salmonella) and involves T3SS, injects Yops into cells – produces heat-stable enterotoxin
Diagnosis of Y. enterocolitica
Stool culture
Treatment of Y. enterocolitica
Self-limiting (supportive therapy)
C. diff characterisitics
Gram+ anaerobe, non-invasive, SPORE-FORMING, emerging pathogen
Disease/symptoms of C. diff
Causes pathology in the COLON – varies a lot – asymptomatic carriage is least severe, CDAD, pseudomembrane colitis, most severe is fulminant colitis (causes necrosis) leading to toxic megacolon
Asymptomatic C. diff carriage
No adverse affects
C. diff associated diarrhea (CDAD)
Causes watery diarrhea with fecal leukocytes and sometimes occult blood; symptoms include nausea, anorexia, fever, malaise, dehydration, leukocytosis with left shift; abdominal distension and tenderness are seen; sigmoidoscopic exam shows diffuse or patchy nonspecific colitis
Pseudomembrane colitis (C. diff)
Same as CDAD but more severe – sigmoidoscopic exam shows raised, adherent yellow plaques (hence name pseudomembrane)
Fulminant colitis (C. diff)
Severe or diminished diarrhea (surgical consult is required); lethargy, fever, tachycardia, dilated colon; can present as acute abdomen (sharp pain); no sigmoidoscopic exam should be performed
Pathogenesis of C. diff
Toxin A and B cause damage to the mucosa and disrupt host cell cytoskeleton
Epidemiology of C. diff
Often a hospitalized patient will be exposed to C. diff and if their gut flora is altered (ex. by antibiotics) they can acquire it
Diagnosis of C. diff
Detect toxin in stool (culture not helpful)
Treatment of C. diff
Oral vancomycin or metronidazole
Prevention of C. diff
Fecal transplant
EHEC (E. coli) characteristics
Infection of the large intestine – Gram- facultative anaerobe, found in animal reservoirs
Epidemiology of EHEC
Sporadic cases in developed world mostly to do with hamburger or vegetables (eHec for Hamburgers)
Disease of EHEC
Hemorrhagic colitis (eHec for Hemorrhagic) that causes bloody diarrhea and abdominal tenderness but no fever
EHEC sequelae
Hemolytic uremic syndrome (HUS) – anemia and kidney failure
Pathogenesis of EHEC
AE lesions like EPEC (Type III secretion using Tir), Shiga-like toxin that blocks translation by cleaving part of the 60S subunit of ribosome
How does EHEC cause kidney damage?
Glomeruli are rich in toxin glycolipid receptor Gb3 so toxin can bind and target those tissues –> kidney damage –> kidney failure sometimes
Diagnosis of EHEC
Presumptive due to bloody diarrhea without fever (can also use culture, PCR to detect Shiga toxin, or rapid diagnostic test kits)
Treatment of EHEC
Supportive therapy, not antibiotics
Why are antibiotics often contraindicated for EHEC?
Bacterial cell damage will lead to a lysogenic phage –> lytic lifecycle that increases toxin production and might increase HUS rate
Prevention of EHEC
Properly cook hamburger, cook raw vegetables
Shigella spp. characteristics
Gram- rods, facultative anaerobes, intracellular pathogens (very acid tolerant), cause dysentery – INFLAMMATORY
Epidemiology of Shigella
Humans are only reservoir, transmission through fecal oral route (breakouts in daycares), incidence is directly related to hygiene, very low infectious dose needed
Clinical manifestations of Shigellosis
1-3 post-ingestion, disease usually self-limiting 2-5 days post
Strain specificity of Shigella
S. sonneii – fever, malaise and watery diarrhea
S. flexerni and S. dysenteriae – lead to dysentery and other typical symptoms, frequent bloody/pus-filled stools (S. dys has potential for HUS)
Pathogenesis of Shigella
Very acid resistant, invades macrophages through M cells, escapes quickly from phagosome and induces apoptosis (inflammation and pus production) – interacts with basolateral face of enterocytes to induce uptake via T3SS and cause lysis of endocytic vacuole – invades other cells with actin polymerization
Shiga toxin production (Stx) in Shigellosis
Binds host Gb3 receptor, inhibits translation –> cell damage –> tissue damage – glomerular endothelial cells are rich in Gb3 which is why this causes HUS
Diagnosis of Shigella
Stool culture, serological tests to confirm
Treatment of Shigella
Rehydration therapy, antibiotic treatment (if necessary but ampicillin resistance is common)
Prevention of Shigella
No vaccine, just improved sanitation – infection does not make you immune
EIEC
Another E. coli, infects large intestine – same as Shigella except no Shiga toxin
