10 - Bacterial Infections of the GI Tract Flashcards
Which gut bacteria cause systemic disease and penetration through an intact mucosa?
Listeria and Salmonella typhi
Which pathogens invade cells/cause inflammatory or cytotoxic destruction of the ilial or colonic mucosa?
Shigella, enterohemorrhagic E. coli, nontyphoidal Salmonella serotypes, and campylobacter/helicobacter
Which bacteria causes a shift in bidirectional water and electrolyte fluxes in the upper small bowel by intraluminal toxins or minimally invasive organisms?
Vibrio cholerae.
What is the ultrastructure of the small intestine? What type of cells are present?
Villi are sites of terminal digestion and absorption.
Mucus produced by goblet cells for protection and lubrication.
Vili and crypts lined by single layer of columnar epithelial cells.
Describe the ultrastructure of the large intestine? What type of cells are present.
Absorbs most water from chyme and compacts material into feces.
Vili are absent, but the colonic mucosa is fill of crypts of lieberkhun that are make of columnar epithelial cells.
How much fluid enters the GI tract each day? What is the avg fecal excretion each day? Where does 90% of net absorption occur?
8.5 L of fluid enters the GI tract each day.
Avg daily fecal excretion is about 150 mL (requires absorption of 8L)
90% absorption occurs in small bowel (lg intestine can’t absorb more than 2-3 L a day)
What are the six barriers to invading pathogens?
- Epithelial barriers and intestinal motility: rapid epithelial turn over
- Structural barrier: adherins and tight junctions
- Chemical barrier: gastric acidity
- Paneth cells (in crypts): secrete AMPs like lysozyme and a-defensins.
- Adaptive immunity: MALT makes IgA
- Microbial recognition: PRRs recognize bacterial PAMPs.
What is the role of normal commensals? When do we get them?
- Colonize neonates following delivery; drives maturation of mucosal immune system
- Monopolizes physical and nutritional niches at mucosal surface
- Contributes to nutrient acquisition by fermenting non-digestable dietary components; synthesis of VitK and B
- Provides host defense to limit ability to pathogens to take-up residence and invade the human body
What are the characteristics of listeria monocytogenes? What is the organism associated with this? In what conditions does it grow?
Aerobic, non-spore forming gram + rod.
Motile at room temp; tumble in solns.
1-45 C and high salt concentrations.
In what populations is listeriosis found in humans? How does it cause disease?
- Neonates
- Elderly
- Pregnant women
- People with defects in cellular immunity
Penetration through intact mucosa to the reticuloendothelial system.
What is the pathogenesis of listeria? How does it replicate?
- Can survive stomach acid and bile salts.
- Adherence to host cells via InIA, internalin.
- Enters enterocytes in peyers patches
- pH drop in phagosome activates listeriolysin O and PLC
- Bacteria replicate in cytoplasm; ActA located on one pole of bacterium and polymerizes host actin for movement to get to new uninfected cell to repeat process.
- Systemic effects occur with entry into macrophages and spreading through reticuloendothelial system (sleen, liver).
What is the epidemiology of listeria? How is it spread?
Sporadic and associated with undercooked means, unpasteurized milk, and contaminated cheese, and unwashed raw vegetables.
Can grow in wide range of temps, even during prolonged refridge.
Human to human transmission occurs from mother to child.
What is the clinical appearance of listeria in neonates?
Early onset in utero: abortion, stillbirth, premature birth.
Granulomas may form in organs
Late onset: 2-3 wks after birth, characterized by meningitis or meningoencephalitis with septicemia.
What is the clinical appearance in pregnant women? What about in healthy and immunocompromised adults?
Pregnent: usually during 3rd trimester when cellular immunity most impaired; influenza like symptoms with fever
Adults: Healthy-mild flu-like illness, self-limited gastroenteritis. Immunocompromised-meningitis, high mortality and neurological disease.
How would you diagnose listeria in the lab?
Gram stain CSH for meningitis pts - 10^4/ml to detect
Culture 1-2 days, cold enrichment in fridge
Biochem or serological tests for 13 serotypes.
Pulse-field gel electrophoresis.
What is the treatment and prevention for listeria?
Control difficult because it’s in environment. No vaccine.
High risk individuals should avoid: raw or partially cooked food from animals, soft cheese, unwashed raw vegetables.
Treatment: gentamicin w/ penicillin or ampicillin (naturally cephalosporin resistant).
What is the prevalance of salmonellosis in the US?
1 million cases/year
19,000 hospitalizations and 380 deaths
What are the characteristics of salmonella? What does it do in the body?
Gram - rod found in soil, water, and intestinal flora.
H antigen: for flagellar proteins
K and Vi capsular antigens: for E. coli and S. typhi respectively
O antigen for LOS.
Penetration through intact mucosa and inflamm or cytotoxic destruction or colonic mucosa.
Does not ferment lactose
What is the host range of salmonella? What is it resistant to?
Broad range: birds, mammals, reptiles, rodents EXCEPT typhi and paratyphi which are highly adapted to humans
Can resist stomach acid and can invade M cells and enterocytes in peyers patches.
What is the pathogenesis of salmonella?
Once it invades the mucosa, it replicates within the endocytic vacuoles, which are modified and stabilized by the injection of bacterial proteins through type III secretion systems (spacious vacuole).
Pathogenicity island 1 genes: invasion (SPI-1)
Pathogeniticy island 2 genes: evasion of immune response
What is the clinical appearance of gastroenteritis due to salmonella caused by serotypes other than typhi and paratyphi?
6-48 post eating contam food.
Nausea, emesis, non-bloody diarrhea. Fever, abdominal cramps, headache.
Symptoms can persist 7-10 days, spontaneous resolution.
What is the epidemiology of the gastroenteritis caused by salmonella? Who is most likely to get it? (this is only for serotypes other than typhi and paratyphi).
From contaminated food such as poultry, eggs, dairy products, and ground beef. (or pet turtles!)
Incidence greatest in children under five and adults older than 60.
Freq during summer months.
High infectious dose.
What is the pathogenesis or enteric or typhoid fever?
Invade cells and replicated as in gastroenteritis.
Typhi also replicates in macrophages and spreads through the reticuloendothelial system to liver, spleen, blood, and BM.
Bacteremia causes fever and may lead to localized infections (osteomyelitis, endocarditis, arthritis) or rarely in bowel perf.
For typhoid/enteric fever, what is the inoculum? How is it transmitted? Where is it endemic?
Inoculum for Typhi is low (this differs from the non-infectious salmonella).
Transmission is person to person and fecal.
Endemic in India, south/central America, Africa. Travelers should be vaccinated.
What are the three clinical diseases associated with salmonella?
Salmonella gastroenteritis
Salmonella septicemia
Enteric fever
What are the symptoms of salmonella gastroenteritis?
Symptoms for 6-48 hrs after food consumption.
Fever, cramps, myalgias, headaches, nausea, emesis, and non-bloody diarrhea.
Symptoms for 2-7 days but self limiting.
What species are associated with salmonella septicemia? Who is at risk?
ALL SALMONELLA SPECIES CAN CAUSE A BACTEREMIA.
But, they generally don’t unless you have a compromising condition like HIV or age extremes.
What are symptoms of enteric fever caused by salmonella typhi?
10-14 days after ingestion, gradual fever, headache, myalgias, malaise, anorexia, rose spots (bacteremic phase).
After bacteremic phase GI symptoms occur (GI phase)
Colonization of gall bladder and reinfection of the intestines.
How do you diagnose salmonella in the lab? What are some properties of it?
Stool culture using selective medium.
Lactose -, motile, makes H2S (makes dark black colonies)
Also can use pulse electrophoresis.
What is the treatment for salmonella?
Symptom relief, no Abx for gastroenteritis.
Ampicillin, trimethoprim-sulfamethoxazole or ciprofloxacin for systemic infections.
How can travelers be protected from salmonella?
Live attenuated vaccine: Ty21a good for 5 yrs, 6 capsules every other day, booster at 4 yrs. Not for <6 yrs.
Typhim: Vi polysaccharide capsular vaccine, not for kids under 2 yrts.
What are characteristics of shigella?
Family member of enterobacteriacaea.
Gram negative and non-motile.
Infectious dose is low.
What are the four recognized biogroups of shigella?
Dysenteria, flexneri, boydii, and sonnei
What is the pathogenesis of shigella?
- Invades M cells in peyers patches. Replicate intracellularly in colon.
- Inject type III effectors called Protein Antigens into cells to instruct the cytoskeleton to engulf them
- Once inside host cells, it lyses vacuole and replicates in cytoplasm.
- Uses host actin to move and penetrate new cells.
- Induces apoptosis in phagocytic cells which leads to IL-8 release and huge inflamm response.
What do shigella make that induce bacterial uptake?
Ipa proteins that are injected by type III secretion systems.
Secrete shiga toxin A-5B toxin
- A subunits cleaves 28S ribosomal RNA to dirsupt protein synthesis.
- B recognizes and binds host glycolipid GB3
What is the epidemiology of shigella? Who are most likely to get this?
Humans are only reservoir; Shigellosis is a pediatric disease.
Infectious dose is low so person-person is easy through fecal-oral.
S. dysenteriae in Africa and Central America more virulent with 5-15% mortality.
What are the clinical symptoms of Shigella?
Incubation 1-3 days after ingestion.
Cramps, straining to defecate, diarrhea, pus and blood in stool, mucus in stools.
Dysentary - coined my hippocrates to describe blood and mucous in stool.
How is shigella diagnosed in the lab?
Lactose negative colonies on selective medium appear colorless on MacConkey agar.
Shigella is NOT motile while salmonella is flagellated and motile. Shigella does NOT produce H2S while salmonella does.
What is the treatment of shigella?
Milf infections usually self-limiting; Abx rarely used.
Ampicillin, trimethoprim/sulfamethoxazole, ceftriazone.
Antidiarrheal agents make illness worse and can cause shiga toxin build up.
What are the characteristics of Shiga Toxin Producing E. Coli (STEC)? What is another name for this?
Enterohemorrhagic E. coli (EHEC).
Family member of Enterobacteriaceae; gram -. Low infectious dose.
What is the pathogenesis of Shiga-toxin producing E. coli (STEC)?
Cytotoxic to Vero cells : vero toxin
Toxic activity could be neutralized with antibodies to shiga toxin.
Produce distinct histopathology called attaching and effacing lesion.
EPEC=STEC for the attaching and effacing lesion but do NOT make shiga toxins.
EDIT LATER IM CONFUSED ABOUT THIS
How does enterohemorrhagic E. coli differ from Shiga-toxin producing E. coli?
EPEC = STEC for the attaching and effacing lesion but do NOT synthesize shiga toxins.
EDIT FOR CLARITY
What is the mechanism by which STEC invade?
Alterations in the cellular sytoskeleton are due to effectors injected by the bacterial type III secretion system.
Injects protein called Tir which integrates into the cell membrane and binds bacterial OM protrin called intimin.
Bacteria grow in place and release shiga toxin.
What encodes shiga toxins? What are the two different types?
Encoded on lysogenic bacteriophase in E. coli.
Stx1 = shiga toxin Stx2 = 60% homology to Shiga toxin (A-5B) shiga-like toxin
Strains expressing both strains are more virulent.
What is the function of shiga toxin?
Strops host protein synthesis by cleaving host ribosomal RNA.
Binds cells with GB3 receptors.
Stimulate expression expression of inflammatory cytokines.
What serotypes are associated with shiga-toxin producing E. coli? What is the infectious dose?
O and H serotypes usually.
Some may be selected for in the intestinal tract of cattle and can spread via cattle feces.
Low infectious dose.
What are symptoms of hemorrhagic colitis?
Severe abdominal pain and bloody diarrhea 3-4 days after ingestion.
Vomiting in 50% of patients, no fever.
What are symptoms of hemolytic uremic syndrome (HUS)? Who gets it?
OCcurs in 5-10% of children under 10.
Acute renal failure, thrombocytopenia, hemolytic anemia.
How is STEC diagnosed in the lab?
Culture: differential identification on inability to ferment sorbitol (sorbitol-containing MacConkey agar)
Colorless colonies.
Commercial immunoassays used to directly detect presence of Stx-1 or Stx-2
What is the treatment for STEC?
Supportive care and monitoring complications.
Antiperistaltic agents can increase the risk of systemic complications.
Antibiotics not recommended because in experimental students they increased the shiga toxin production.
What are the characteristics of campylobacter? What are the major isolates?
Gem negative curved rod; spiral or comma shaped.
42 degrees, motile.
C. jejuni, C. upsalensis, C. coli, and C fetus.
What symptoms does campylobacter cause in the intestines?
Inflammation: GI infections produce damage to mucosal surfaces of jejunum, ileum, and colon.
PMN infiltrate in mucosa and submucosa causing ulceration.
What diseases can develop from campylobacter?
Autoimmune disorders, guillain-barré, reactive arthritis.
May be due to cross-reactivity of some campylo. LPS and peripheral neural tissue gangliosides.
What is the epidemiology of campylobacter? When is it more common?
Associated with contaminated chicken, raw milk, and pets.
More campylobacter causes in the US (2 mil/yr) than salmonella and shigella combined.
Summer and early fall most common.
__________ colonized and is acquired from domestic dogs.
Campylobacter upsaliensis
How do campylobacter infections present clinically? What can C. fetus cause?
GI infectoins - acute enteritis characterized by blood y stools, inflammation, ulcerated mucosa.
Chronic diarrhea in immunocompromised.
C. fetus can cause systemic or extraintestinal infections in compromised pts which is resistant to serum Ab killing.
How would you diagnose Campylobacter in the lab? Why is it hard to culture?
Microscropy for darting motility in fresh feces, S-shaped, presence of RBCs and WBCs in stool.
Antigenic detection.
Hard to culture due to slow growth, requires selective medium, microaerophilic, and high incubation temps.
How is campylobacter treated?
Fluid replacement.
Severe: azithromycin or erythromycin.
What are the characteristics of H. pylori?
Gram negative curves rods.
Multiple polar flagella, highly motile.
Produce powerful urease enzyme that converts urea into NH3 and CO2.
Gastric colonization from H. pylori can be ________?
Lifelong, so part of the pathogenesis involves survival in this extreme environment.
How does H. pylori survive in the acidity of the stomach? What do they do once theyre in the stomach?
- Urease allows bacterium to survive acidity
- Swim through mucus w/ flagella
- Adhere to gastric epithelium via receptors that include lewis blood-group Ags and laminin
- pH at epithelial surface is 7.0
The production of peptic ulcers from H. pylori is strongly correlated with what? What is the first of these?
Two genetic loci.
One encodes toxin VacA, which forms anion-specific channels that form large vacuoles in cultured cells.
Alters tight junctions and induces epithelial erosion.
Besides VacA, what else made by H. pylori is strongly correlated with peptic ulcer production?
Second genetic locus that encodes genes:
-Type IV secretion system that injects CagA, which induces IL-8 release and products that increase IL-8 transcription.
Type IV effectors also induce pedestal formation.
What is the epidemiology of H. pylori? What diseases is it associated with?
Humans are only reservoir.
Asymptomatic in 70-80%.
Associated with gastric adenocarcinoma and gastric B-cell lymphomas.
What is one postulation about why H. pylori is assocaited with gastric adenocarcinomas and gastric B. cell lymphomas?
Thought that chronic inflammatory response may contribute to the development of cancer.
How is Helicobacter diagnosed in the lab?
- Urea breath test
- Histologic exam of gastric biopsy
- Biochem detection of urease activity from gastric biopsy
- Detection of antigens from stool
What is the treatment and prevention for helicobacter?
Treat: proton pump inhibitor + macrolide + B-lactam
No vaccine.
What are characteristics of Vibrio? Which types makes a toxin?
Gram negative curved rods, not part of family of enterobacteriaceae.
Vibrio Cholerae serogroups 01 and 0139 produce cholera toxin; these serogroups are associated with epidemic disease and are based on LPS.
What is the structure and physiology of vibrio cholera?
Requires NaCl for growth, oxidase +, toxin co-regulated pilli.
Curved rods with single polar flagella.
Serotype 01 subdivided into classical and El Tor biotypes.
What is the mechanism of action of Cholera toxin?
A-5B protein encoded by bacteriophage.
Toxin binds ganglioside receptors, GM1, on intestinal epithelial cells.
A-subunit ADP ribosylates Gs and induces cAMP, causing water efflux (up to 20L/day).
What is encoded on the vibrio cholerae genome?
TCP: toxin coregulated pilus used to adhere to mucosal epithelium and used by phage to infect bacteria.
What is coded on the vibrio phage?
Zonnula occludens toxins (ZOT) - disrupt tight junctions
Accessory cholera enterotoxin (Ace) - increases fluid secretion
Chemotaxis proteins.
Expression of toxins prevents the development of live attenuated vaccines.
What is the epidemiology of cholera?
3-5 million worldwide.
Transmitted by contam. water and food.
Infectious dose is 10^8.
V. parahaemolyticus and V. vulnificus are transmitted with uncooked oysters and in pts with hepatic disease.
What symptoms does vibrio cholera cause? What is the mortality if left untreated?
2-3 days after ingestion - water rice-water diarrhea.
Fluid and electrolyte loss leads to dehydration, cramps, metabolic acidosis, and hypovolemic shock with cardiac arrhythmia and renal failure.
60% mortality when untreated.
How do you diagnose cholera in the lab?
Microscopy for gram - rods in large numbers in stool.
Culture - relatively easy to isolate in lab
What is the prevention of V. cholera?
Vaccines:
- formalin inactivated whole cell vaccine (IM).
- heat and formalin killed 01 classical and El tor strains: IgA response prevents colonization
- Non-toxic B subunits - IgA response prevents toxin binding
What is the treatment for V. cholera?
Fluid/electrolyte replacement.
Abx can reduce toxin production.
