bacterial infections of the GI tract Flashcards
Ultrastructure of the small and large intestine
The villi are the sites of terminal digestion and absorption of nutrients thru absorptive enterocytes. Mucus is produced by goblet cells for lubrication. Mucosal villi and crypts lined by one layer of epitheliat cells. Large intestine absorbs most of the water from the chyme (digested material from small gut) and compacts into feces. No villi in large but full of Crypts of Lieberkhun (similar to small intestine)
Fluid balance
we take in 8.5 L of water, fecal excretion is about 150 ml, so we need to absorb 8 L of water. 90% of absorbion happens in small gut. A shift of the flow of water (flux) leads to diarrhea.
Infections alter normal physiology in one of three ways:
- Penetrate mucosa
- inflammation or cytotoxic destruction
- Shift in bidirectional water and electrolyte fluxes
Barriers to invading pathogens
- Epithelial barrier and intestinal motility (rapid shedding of epithelium, antimotility drugs can prolong infections)
- Structural barriers (adherens and tight junctions glue together the epithelium to avoid stuff getting in)
- Chemical barrier (pH kills stuff in the stomach)
- Paneth cells (differentiated cells that secrete antimicrobials)
- Adaptive immunity (MALT, IgA, DCs, M etc)
- Microbial recognition (PRRs recognize PAMPs)
Role of normal commensal organisms
GI tract is colonized by symbiotes
- neonates colonized immediatly after birth
- Colonization drives that maturation of mucosal immune system
- Intact microbiota monopolizes nutrients on mucosa
- Normal microbiota contributes to nutrient acquisition by fermenting
- microbiota defends against pathogenic microbes
Listeria
Cantalope, frozen or fresh veggies, raw milk, soft cheeses, packaged salads
Penetration thru intact mucosa to the reticuloendothelial system- causes Listeriosis by way of L. monocytogenes
its an aerobic, non-spore forming gram positive rod
can grow at varied temps, and in salt, tumbles in solution, weakly hemolytic
Human disease- restricted to well defined population. (young, old pregnant, immuno comp)
Listeria pathogenisis
eat bad food, listeria is able to survive in stomach acid and bile salts. Adheres to host cells with internalin (InlA). Enters eneterocytes or M cells in Peyer patches. Phagosome is intact until pH drops signaling listeriolysin O and phospholipase C. Bacteria replicate free in the cytoplasm. ActA located on one pole of bacteria polymerizes host actin and causes it to shoot itself into another cell. Systemic infection begins when a macrophage gets infected and spread thru the reticuloendothelial system (meningitis)
Listeria Epidemiology
sproadic, contaminated foods, found in fecal matter of animals, can grow in frige, human to human transmission from mom in utero
Listeria clinical disease
Neonatal Disease: early onset disease-> abortion, granulomatosis infantseptica-> granuloma in multiple organs, Late onset-> meningitis etc after a few weeks
Pregnant women: usually during third trimester when immunity is most impaired flu like symptoms
Adults: if healthy flue like, if immuno comp: meningits and death
Salmonella
penetration thru an intact mucosa to the reticuloendothelial system and inflammatory or cytotoxic destruction of ilium or colon mucosa
Member of enterobacteriaceae fam
Gram negative rods found in soil, water, normal flora
Serotyping to id isolates (many…do not ferment)
H Ag= flagellar proteins
K or Vi= capsular Ag for E. coli and S. typhi
O antigens= LPS
Salmonella pathogenisis
Broad host range except for typhi and paratyphi which are human specific
S. resists stomach acid, attaches to mucosa of small intestine and invades microfold (M) cells and enterocytes in peyer patches
S. replcates in endocytic vacuoles (which are modified by bacterial proteins =spacious vacuole)
Pathogenticity island genes (1= invasion, 2= evasion of Imm sys)
Gastroenteritis of salmonella
infection and rep induces inflammatory response-> disruption of the enterocytes and malabsorption, release of prostaglandins, stimulation of cAMP and fluid secretion
going to present as gastroenteritis (6-48 h post eating contaminated), nausea, vomiting, and non bloody diarrhea, etc. symptoms persist 7-10 days and spontaneous resolution
Gastroenteritis due to salmonella epidemiology
inflammatory or cytotoxic destruction of the ileal or colonic mucosa
due to ingestion of contaminated food, young and old, summer months, raw meats, infection dose is high
SalPathogenisis of Enteric or typhoid fever
bacteria invade cells and replicate as in gastroenteritis, typhi also replicates in macrophages and spreads in reticuloendothelial system
bacteremia causes the fever and can lead to suppurtive in fection or perf of intestine
Enteric or typhoid fever epidemiology
relatively low inoculum for typhi, transmission person to person fecal, endemic in india, africa, travelers need to be vaccinated
salmonella clinical disease
gastroenteritis, salmonella septicemia, all salmonella can cause septecemia, enteeric fever after 10-14 days. diagnosed in stool culture, H2S
Salmonella treatment
symptomatic releif (fluids but no antibiotics for s. gastroenteritis.
Careful food prep
Ampicillin, azole, floxacin for systemic infections
Travlers : live attenuated vaccine, and capsular vaccine
Shigella
pathogen that invades cells/cause inflammation/intoxicate
family member of enterobacteriacae (gram -) non motile, doesnt ferment, no capsule, innocuous does low, very contagious (fecal oral, 4 biogroups)
Shigella pathogenisis
Invade M cells in peyer’s patches, they replicate intra cellularly in the colon. Bacteria inject type 3 effectors into cells to instruct the cytoskeleton to engulf them. Effectors are called invasion Protein Ag or IpaA, IpaB-C-D
Humans make Ab against them, once inside cells, bacterium lyses vacuole and relicates in cytoplasm. Polymerize host actin to move membrane to penetrate uninfected cells. Shigella induce apoptosis in phagocytic cells-> IL-1 -> intense inflammatory response
Shigella pathgogenisis
Ipa proteins induces bacterial uptake, injected by the type 3 secretory system
Shigella secrete shiga toxin
exported by a type 2 secretory pathway (not injected but exported)
Shiga toxin is A:5B toxin
B= binding
A= enzymatic activity cleaves 28 s ribosomal RNA->colonic epithelium death and cells and mucous are lost from the large intestine
Shigella Epidemiology
Humans are the only reservoir, Sflexneri predominates, its a pediatric disease, inocuos dose low fecal oral transmission, s. dysentariae (very virulent)
Shigella clinical disease
Incubation period after 1-3 days symptoms (ab cramps, tenesmus (defecations, pus blood neutrophils and mucous in stool
lab diagnosis: lactose negative that appears as pink, not motile
mild infections (ampicillin, azoles, axone)
imodium can be bad
STEC shiga toxin producing E. coli aka enterohemorrahagic E colu (EHEC)
family of enterobacteria, infection dose is low, member of e coli family
STEC pathogenisis
culture filtrates these bacteria were cytotoxic to vero cells
toxins are nuetralized with shiga toxin antibodies
produce attaching and effacing lesions
Epec=Stec fothe the attaching and effacing lesion but dont make shiga toxin
shiga toxins located on lysogenic bacteriophage in e coli stx1 and stx2 strains with bothare more virulent
only O and H serotypes is bad (comes from cattle) infectious dose is low
Stec clinical disease
hemmorrhagic colitis is characterized by bloody diarrhea, hemolytic urine syndrome
lab diagnosis: sorbitol, supportive care
Campylobacter
gram negative spiral or comma shaped, motile
inflammation of colon
infection associated with autoimmune Guillain Barre syndrome (thru contaminated material
Helicobacter
gastric juice doesnt kill it
gram negative curved rods, lifelong
peptic ulcers with VAcA toxin, and CagA
vibrio
o1 and o139 cholera toxin thru oysters
