illustrations of bacterial pathogenicity - GI tract

Question 1

give 3 examples of food poisinings

Answer 1

1 - clostridium botulinum toxin from anaerobic growth in food
2 - staphylococcus aureus, enterotoxins, bacteria ingested but not colonised
3 - clostridium perfringens - germinates from spores in food and toxins produced in intestine.

all 3 caused without host colonisation

Question 2

cause of botulinism

Answer 2

clostridium botulinum - toxin during anaerobic growth in food ie home canned foods. toxin absorbed from stomach. cleaves the neuronal snare synaptobrevin. acts at NMJ so flaccid paralysis.
Rare but deadly.

Question 3

describe staphylococcus aureus poisining

Answer 3

grows in custard and processed meats at room temp from human carrier contamination.
heat and acid stable enterotoxinsinteract with gastric mucosa. could be superantigens in blood.
no colonisation.

Question 4

describe clostridium perfringens poisining

Answer 4

germinates form spores in preheated food. ingested produces toxins that interact with mucosa and may be superantigens

Question 5

characteristics of gastroenteritis

Answer 5

nausea, vomiting, diarrhoea, abdominal pain

Question 6

what’s dysentry?

Answer 6

inflammatory GI disorder. blood and pus in feces, pain , fever and cramps. usually disease of colon

Question 7

cause of cholera

Answer 7

vibrio cholerae colonizing the intestinal epithelium.
spread fecal-oral
acute infection, 50% mortality but electrolyte replacement reduces to 1%.

Question 8

how does vibrio cholerae colonize?

Answer 8

fimbrial adhesin
cholera toxin genes carried on a bacteriophage in the chromosome and coregulated with adhesin and other genes by a HAP signal (global).

Question 9

how does cholera toxin act

Answer 9

AB5 structure
B binds receptor GM1-ganglioside
receptor mediated endocytosis and retrograde to ER.
Active A into cytosol.
ADP ribosylates Gs, stuck on, uncontrolled high cAMP.
disturbance of NA and CL CFTR membrane pump.
increase CL out, decrease NA in.
leads to water and electrolyte loss of 12-20 L per day into lumen.
‘rice water’ diarrhoea, shock, collapse, sometimes cardiac failure.

Question 10

cause of dysentry

Answer 10

shigella species

locally invasive, inflammatory disease of the large intestine (Colon)

Question 11

result of dysentry

Answer 11

mucosal ulcers, vascular damage. low vol diarrhoea with blood, mucus and PMNs.
v infectious, only need 100 bacteria vs millions for cholera. person to person or food transmission.

Question 12

pathogenesis of dysentry

Answer 12

resist stomach acid by outer membrane proteins
travers colon mucosa via phagocytic M (microfold) cells (antigenic sampler cells with no mucus)
force across BM into mucosal cells by needle complex injecting invasion proteins and interacting with actin.
cytoskeletal changes, bacteria in vacuole.
escape vacuole, inflammation
multiply in cytosol,
actin based motility
spread into adjacent cells via protrusion of membrane then lysis of vacuole.
taken up by macrophages inducing more inflammation but triggers its apoptosis.
host inflammation accentuated by shiga toxin (glycosidase - kills cells by blocking protein synth).
Bacteria killed by PMNs but LPS release therefore more inflamm.

Question 13

what can circulating shiga toxin cause

Answer 13

kidney failure - haemolytic uraemia syndrome, particularly in young children where the AB response is poor.

Question 14

cause of salmonellosis

Answer 14

salmonella, an invasive intracellular pathogen

Question 15

cause of food bourne gastroenteritis

Answer 15

salmonella enteritidis, S. typhimurium. large animal reservoirs ie chicken eggs

Question 16

pathogenesis of salmonellosis

Answer 16

1 - needle and effectors to host cytoskeletal rearrangement. enter apical surface of epithelia of distal ileum and proximal colon.
2 - remain in membrane bound vacuole
3 - released from epithelial cells possibly by lysis. inflammation mainly by LPS lipid A.
4 - taken up by macrophages, replicate. switches on up to 200 genes to inhibit phagolysosome, defensins and oxidative burst (ie superoxide dismutase)
5 - host response activates cAMP and fluid secretion. hence diarrhoea.

Question 17

cause of typhoid fever

Answer 17

salmonella typhi
no animal reservoir.
replicate in macrophages, travel via blood to liver and spleen etc.
severe symptoms due to LPS lipid A.
shed into the bile to intestine and out.
carriers ie typhoid mary where it is quiescent then recurrent reemergence.

Question 18

types of E.coli capable of diarrhoeal diseases

Answer 18

1 - ETEC - enterotoxic - fimbrial adhesins. produces cholera-like enterotoxin. common cause of travellers diarrhoea. contaminated water.

2 - EPEC- enteropathic - pilus adhesin, retracts to pull bacterium in. deliver effectors via needle inc Tir which binds EPEC’s intimin. generates pedestal. inflammation.

3 - EHEC - enterohaemorrhagic - pili and pedestal like EPEC. inflam accentuated by shiga-like toxin, can also cause renal failure. predom serotype = 0157, often from beef.

other types cause neonatal meningitis and UTI (UPEC). some are harmless flora. consequence of pathogenicity islands.

Question 19

sources of gastroenteritis other than salmonella?

Answer 19

campylobacter (analogous behaviour to shigella).

Question 20

danger with listeria?

Answer 20

normally harmless but can invade like shigella, go systemic, cross the placenta to damage fetus or BB to cause meningitis. inflammation and tissue damage.
danger in immunocompromised

Question 21

cause of antibiotic associated diarrhoea

Answer 21

clostridium difficile
toxin producing, anaerobic, spore forming.
colonises colon following antibiotic eradication of flora. isue in hospitals.
diarrhoea and inflam primarly through 2 toxins that glycosylate small GTPases.
subvert actin cytoskeleton, disrupt tight juncitons, leaky epithelium, tissue damage.
can also be indirect with a pseudomembrane and inflamm

Question 22

a cause of gastric ulcers?

Answer 22

helicobacter pylori - causes about 90% of gastric and duodenal ulcers. up to half of human pop colonised but few experience illness.
infects the antrum

Question 23

pathogenesis of H. pylori

Answer 23

colonize mucin near gastric mucosal cells. v motile with flagella. adhesins. urease to neutralise acid. pH change also reduces mucus viscosity.
- intense mucosal inflam and ulceration. pylori induces IL8 from epithelia to recruit PMNs.
- destruciton by vacuolating cytotoxin VacA.
progression of ulcer by more inflamm, more PMNs, tissue destruction.
- correlation with gastric cancer poss by chronic inflam of bacterial protein CagA which increase epithelial proliferation.