Bacterial Infections of the GI Tract Flashcards
List the innate immune mechanisms that protect the intestinal tract from pathogenic bacteria
- Maintenance of epithelial barriers
- intestinal motility
- Fluid balance
- Cellular Tight Junctions
- Low pH of the stomach
- Antimicrobial peptides
- Localization of innate and adaptive immune components
- Pattern Recognition Receptors
- normal microbiota and commensal organisms
Bactial infections and bacteria toxins alter normal intestinal physiology in one of three ways
- Penetration through an intact mucosa to the reticuloendothelial system: Listeria, Salmonella, Typhi
- inflammatory or cytotoxic destruction of the ileal or colonic mucosa: Shigella, nontyphoidal Salmonella serotypes, Shiga toxin producing E coli, Campylobacter, Helicobacter
Shift in bidirectional water and electrolyte fluxes in the upper small bowel by intraluminal toxins or minimally invasive organisms: Vibrio colerae
Which organisms penetrate the intact mucosa to the reticuloendothelial system
Listeria, Salmonella
typhi
What organisms do inflammatory or cytotoxic destruction of ileal or colonic mucosa
Shigella, non typhoidal Salmonella serotypes, Shiga toxin producing E. coli Campylobacter, Helicobacter
Which organisms cause a shift in bidirectional water and electrolyte flux in the upper small bowel
Vibrio cholerae
Listeria monocytogene
- adheres to enterocytes and M cells via lnIA, internalin
- escapes the phagosome with listerolysin O and phospholipase C enzymes
- replicates in the cytooplasm
- polymerizes actin to push bacteria to uninfected adjacent cells
- systemic infection occurs during infection of macrophage and spread through the reticuloendothelial system
- human disease=neonates, elderly, pregnant women, individuals with defective cellular immunity
- can cause meningitis, death, fetal death
Salmonella gastroenteritis
- resistance to stomach acid-genetic mechanisms exist, depends on type of food dose of bacteria etc. (so some are resistant some are not)
- entry into M cells and enterocytes using pathogenicity island 1 type II secretion system
- replication within endocytic vacuoles called a spacious phagosome-maintained by pathogenicity island 2, type III secretion system gene products
- entry and replication and type III effectors disrupt enterocytes and cause an inflammatory response, malabsorption, release of prostaglandins, stimulation of cAMP and fluid secretion, fever, headache, nausea, vomiting, non bloody diarrhea
Salmonella typhi
- starts out similar to non typhoidal Salmonellosis (has both type III systems)
- S. typhi replicates in the macrophages and spreads systemically to the liver, spleen, blood and bone marrow
- low infectious dose allows person to person spread
- can cause a chronic infection of the gall bladder, chronic shedding of the organism
- fever (typhoid fever) suppurative infections
Shigella
- type III system encodes effectors that change the cytoskeleton of colonic M cells and facilitate uptake of the organism within a vacuole
- escape from the vacuole is required for intracellular replication
- spread to uninfected cells is facilitated by the ability to use host actin for motility (similar to L. monocytogenes)
- induction of apoptosis leads to IL-1B release and intesne inflammation
- bacteria can make Shiga toxin that halts protein synthesis in cells of the colon
- low infectious dose allows person to person spread
- death of colonic cells results in blood, pus, neutrophils and mucous in stool, abdominal cramps, diarrhea, hence the term dysentery
Shiga toxin producing E coli- also known as Enterohemorrhagic E. coli
- use a type III secretion system to inject Tir, which integrates into the eukaryotic plasma memebrane
- Tir binds to intimin expressed on the E. coli outer memebrane (Tir is almost like a scaffold)
- tight binding of bacteria to cells causes an attaching and effacing lesion
- bacteria grow as microcolonies and secrete Shiga-like toxins
- Shiga like toxin halts protein synthesis and stimulates the production of inflammatory cytokines
- low infectious dose allows person to person spread
- loss of cells can cause a mild uncomplicated diarrhea or progress to hemorrhagic colitis, no fever
- hemolytic uremic syndrom- acute renal failure, thrombocyopenia, microangiopathic, hemolytic anemia
hemolytic uremic syndrom
acute renal failure, thrombocyopenia, microangiopathic, hemolytic anemia
from shiga producing E coli
Campylobacter
- infections cause damage to the mucosal surfaces of the jejunum, ileum and colon and intense inflammatory response can cause ulcers, and neutrophilic infiltrates
- Campylobacter LPS cross reacts with gangliosides in peripheral nerves tissue perhaps leading to autoimmune consequences, reactive arthritis
- cytolethal distending toxin stops cell division
- acute enteritis, diarrhea, blood in stools, fever, abdominal pain, inflammation, ulcerated mucosa
Helicobacter pylori
- Helicobacter are ingested and begin to produce a urease enzyme that locally, neutralizes the pH of the stomach
- flagella allow the organism to swim to a more conducive environment close to the epithelium (where the pH is more neutral)
- they adhere to the epithelium by expressing specific adhesins
-a Type IV secretion system injected CagA, which alters intracellular signaling. Cells form
pedestals and the bacteria replicate, induce IL-8 release and make VacA a toxin that induces gastric erosion
- other bacterial factors induce neutrophil and monocyte migration, chronic inflammation
- gastritis, gastric ulcer formation, gastric adenocarcinoma and B-cell lymphomas
Vibrio cholerae
- bacteria adhere to the mucosal epithelium through the toxin coregulated pilus (TCP) and chemotaxis proteins
- grow to large numbers producing cholera toxin, toxins that disrupt tight junctions, toxins that increase fluid secretion
- cholera toxin binds the GM1 ganglioside receptor and is internalized into cells where it ADP-ribosylates Gs inducing cAMP production, which stimulates chloride secretions and inhibits Na absorption
- The net effect is water efflux, dehydration, electrolyte loss, muscle cramps, acidosis and hypervolemic shock;cardiac arrythmia and renal failure
How does Listeria monocytogenes cause specific gastrointestinal disease
-replication and systemic spread in susceptible individuals
*survives and replicates over a broad range of temperatures and in high salt
• colonizes many animals and contaminates soil
• contaminates many processed and raw foods
• intracellular replication through the coordination of entry, exit from the phagosome and
spread to uninfected cells by actin polymerization
