Lec14 GI pathogens Flashcards
Which bacteria are responsible for foodborn and diarrheal diseases?
- vibrio
- campylobacter
- shigella
- salmonella
- e coli 0157
- listeria
- yersinia
- enterocolitica
parasitic:
- cyclospora
- cryptosporidium
What is path of non-inflammatory diarrhea?
- ingest toxin or organism
- toxin binds enterocyte receptors
- increase the intracellular conc of cAMP/cGMP/Ca
- activate intracellular targets
- alter transport proteins and ion chains
- diarrhea
What is path of inflammatory diarrhea?
- ingest organism
- get intestinal colonization
- mucosal invasion leading to intramucosal multiplication leading to inflammation
- cytotoxins from organism directly cause inflammation
What is mech, location, illness, and pathogen for type 1 enteric infections?
mech: noninflammatory
location: proximal small bowel
illness: watery diarrhea
pathogens:
- vibrio cholerae [primary]
- e coli
- s. aureus
What is mech, location, illness, and pathogen for type 2 enteric infections?
mech: inflammatory
location: colon
illness: dysentery
pathogens:
- shigella [primary]
- salmonella enteritidis [primary]
- campylobacter
What is mech, location, illness, and pathogen for type 3 enteric infections?
mech: penetrating
location: distal small bowel
illness: enteric fever
pathogens:
- salmonella typhi [primary]
- yersinia enterocolitica
What are our enteric defenses?
- gastric aciditiy
- intestinal mobility
- enteric microflora
- immunity
- intestinal receptors
- personal hygeine, host species, genotype
What is the infectious dose?
amount of pathogen needed to cause infection in the host
What is infectious dose shigella vs campylobacter vs vibrio cholerae vs e coli vs salmonella?
shigella 10^2 campylobacter 10^3 salmonella 10^6 e coli 10^8 vibrio cholerae 10^8
don’t memorize this just approximate order
What are micro characteristics of vibrio cholerae?
- curved to straight bacilli
- gram negative
- no spores
150 O [LPS] antigenic serotypes
Which vibrio cholerae serotypes cause cholera
only 01 and 0139
What are the two byotypes of vibrio cholerae?
classical
El Tor
How is vibrio choleare transmitted? What precipates it?
- poor sanitary conditions
- survives in aquatic environment, transmission usually by fecal contamination food/water
- lytic bacteriophages
- asymptomatic carriers
What are clinical symptoms of cholera?
- mild to severe diarrhea
- vomitting
- muscle cramps
- loss of skin turgor
- death from hypvolemic shock, metabolic acidoss, uremia from tubular necrosis
What is the pathogenesis of cholera?
- cholera toxin [ctxAB] carried by bacteriophage
- TCP pili allow attachment and colonization of intestinal villi
- toxin gets secreted by phage
- toxin binds surface receptor of cell and goes into cell
- increases adenylyl cycalse and camp
- get secretory diarrhea Na/H20/Cl/K/HCO3 secreted
What is cholera toxin?
A-B type ADP ribosylating toxin
two types of subunits: ctxA, ctxB
A = enzyme subunits
B = binding subunits
What is treatment for cholera? are there vaccines?
- mainly rehydration
- antibiotics not necessary but can speed up recovery
- vaccines for oral O1 strain and recombinant toxin but efficacy not very good
What is shigella?
- non lactose-fermenting
- small gram neg
- demonstrates agglutinating antibodies
destroys enterocytes
What is group A shigella? disease?
- shigella dysenteriae
- s. dysenteriae serotype 1 causes severe Shiga dysentery
What is group B shigella?
- shigella flexneri
- pediatric shigellosis in developing countries
What is group C shigella?
- shigella boydii
What is group D shigella?
- shigella sonnei
- causes travelers diarrhea, shigellosis in developed and transitional countries
What is the clinical triad for bacillary dysentary [shigellosis]?
- small vol of stool w/ blood, mucus, inflammatory cells
- abdominal cramps and pain
- tenesmus [painful straining to pass stool]
What is the reservoir for shigella? how is it transmitted?
- reservoir is humans
- transmitted person to person
What is pathogenesis of shigella?
- shigella gets into peyers patches and transmitted through epithelial layer of cells
- invades enterocytes from basal layer
- destroys cell cell junctions and by doing so destroys cells
What is shiga toxin?
- produced by shigella dysenteriae
- A is glycosidase subunit inactivates ribosome
- B subunit binds host cell receptor [Gb3]
- contributes to HUS and severity of disease
What are stx-1 and stx-2?
shiga like toxins produced by e coli
have similar affect to shiga toxin
What are the possible complications of shigellosis?
- reactive arthritis [with HLA-B27]
- hemolytic uremic syndrome in infection with shigella dysenteriae
- rarely, bacteremia
What are the micro characteristics of salmonella?
- gram neg rods
- facultatively anaerobic
- motile
- non-spore forming
- do not ferment lactose/sucrose
- produce hydrogen sulfide
Which two salmonella types cause typhoid fever?
salmonella typhi
salmonella paratyphi
What are clinical manifestations of s. typhimurium?
enteritis [diarrhea]
What salmonella type causes bacteremia?
- usually S. typhi
- can rarely get it from s. typhimurium in immunocompromised patient
What are signs of salmonella gastroenteritis?
- nausea and vomiting within 48 hr of infection
- diarrhea
- colicky abdominal pain
- rectal urgancy
- can be mild or can mimic appendicitis, cholesystits, ruptured viscus
What are signs of typhoid fever?
systemic disease with multiorgan dysfunction
- prolonged fever
- sustained blood stream infection without endothelial seeding
During typhoid incubation period [wk 1] what will stool cultures, blood cultures, and widal test show?
- positive stool cultures
- negative blood and widal
During typhoid active invasion [wk 2] what will stool cultures, blood cultures, and widal test show?
stool: negative
blood: 80% positive
widal: 20% positive
During typhoid established diseases [wk3] what will stool cultures, blood cultures show?
stool: 80% positive
blood: negative
During course of typhoid when will blood cultures be positive?
- only positive during wk2 active invasion
- negative during incubation and after established disease
What is source of non-typhoidal salmonella infections?
eating: eggs, chicken, beef, turkey, dairy, salads
pets: iguanas, lizards, snakes
What is the pathogenesis of salmonella?
- oral ingestion
- salmonella pathogenicity island SPI1 codes for injection apparatus
- salmonella forms injection apparatus and secreted effector proteins directly from bacterial cytoplasm to epithelial cell
- salmonella then invade intestinal cells, forces itself to be internalized by non-phagocytic cells and lie in vacuole there
- SPI2 creates another injection apparatus, prevents fusion of vacuole containing salmonella with lysosome, allows protective environment for salmonella to proliferate in cell
- gets in there without causing much damage then proliferates and eventually kills cell
- acute inflammatory response causes diarrhea
What is salmonella
- common in gram neg bacteria
- area of genome that
- there are 2
1st secretes 40 diff genes
2nd has similar appartus but different effector molec
salmonella pathogenicity island 1 codes for injection apparatus, secretes effector molecules from bacterial cytoplasm to epithelial cell
What is function of effector proteins that salmonella secretes?
[SPI1] - rearrange cytoskeleton - trigger cell entry - apoptosis - loss of electrolytes - inflammation [SPI2 I THINK] - systemic spread - proliferation in host organs - intracellular prolieration
What is theory why s. typhi causes typhoid fever
typhi has different pathway for modifying LPS
capsule looks different, once it gets inside typhi will not have strong immune response = flies under the radar, typhimurium will have stronger immune response
What is main route of infection campylobacter?
- handling or consumption of chickens
- little person to person transmission
What is pathogenesis of campylobacter?
- perijunctional adherence
- pre invasion bacterial host cell cross talk
- formation MT based membrane extension of bacteria into cell
- endocytosis of bacteria into cell
- vacuole passage
- exocytosis of bacteria on basal side of cell
- basolateral reinvasion of bacteria into epithelial cell
- CDT induced cell death and release of IL-8
- uptake of bacteria into monocyte/macrophage
what pathogenic factors found genomically for campylobacter?
no real reason found why its so pathogenic
What are treatments for campylobacter?
- self limited disease
- treat if high fever, blood stool, pregnant, immunocompromised, illness more than 1 wk
What is guillain-barre syndrome?
potential side effect of campylobacter
make you paralyzed
immunological over-reaction cross reacts with myelin
What is helicobacter pylori?
associated with gastric and duodenal ulcers
What are the clinical signs of h pylori?
- most infections asymptomatic
- can cause gastritis, gastric ulcer, duodenal ulcer
- linked to gastric adenocarcinoma and MALT lymphoma
How is h pylori detected?
- use bile salts for selective culture
What type of plating do you use to detect salmonella typhi?
bismuth sulfite agar
What type of plating do you use to detect vibrio?
TCBS [thiosulfate-citrate-bile salts]
How does salmonella typhi differ from non-typhoid strains? [citrate, ornithine decarboxy, urea, lysin decarboxy, lactose]
typhi is: citrate - ornithine decarboxylase - urea - lysin decarboxylase + lactose -
non typhoid is: citrate + ornithine decarboxylase + urea - lysin decarboxylase + lactose -
When do you treat in vibrio, campylobacter, salmonella, shigella?
vibrio - don’t treat
campylobacter - don’t treat
salmonella - treat in some circumstance, with sickle cell disease get systemic inflammation in bones
shigella - tend to treat because get such high fevers
What type of antibiotics do you [very generally] use to treat GI pathogens?
- fluoroquinolones [cipro, levo]
- 3rd gen cephalosporins [ceftriaxone]
- macrolides [azithromycin]
- resistant to amoxicillin, 1st gen cephalosporins, and trimethoprim-sulfamethoxazol
