Julian Rood He doesn't even go here

Question 1

Clostridium genus

Answer 1

GP anaerobic that form heat resistant endospores

Pathogenesis involves formation of protein toxins

Question 2

Pathogenic clostridia

Answer 2

Neurotoxic:
Tetani (tetanus) and botulinum (botulism)
Enterotoxic:
Perfringens (food poisoning) and difficile (pseudomembranous colitis)
Histotoxic: signficant tissue damage (muscle)
perfringens (gas gangrene) and septicu (atraumatic gas gangrene)

Question 3

Gas gangrene

Answer 3

Perfringens
Highly invasive, histotoxic - ischaemic tissue
Contamination of wounds in surgery/war
Gas production in lesion (H2 and Co2)
a toxin: phospholipase C - hydrolyses membrane phospholipids (1st bacterial toxin shown to be an enzyme) - acts on phosphatidylcholine –> unstable membrane

Question 4

alpha toxin

Answer 4

alphahelical domain (binds zinc): phospholipase C domain

and beta sheet domain (binds calcium)
involved in toxicitiy - lipid binding component

essential for disease:
plc mutant OK

Question 5

C DIFFICILE

Answer 5

Enterotoxaemic infections

Nosocomial - most severe form is pseudomembranous colitis (inflammatory response - pus)

Question 6

c diffile cause disease?

Answer 6

antibiotic treatment leads to disruption of normal flora
C.difficile SPORES invade hospital environment
2002 epidemic strains/hypervirulent
2010 arrived in australia

Question 7

Toxins A and B c difficile

Answer 7

Monoglucosyltransferases
Glucosylate Rho family of proteins
Disrupt actin cytoskeleton
Autocatalytic - cleaves itself
Binding component binds to receptor on cell surface --> endocytosis --> toxin in endosome --> endosome acidified --> conformational change --> catalytic protease domain is active

Question 8

Toxin B

Answer 8

essential for virulence

Question 9

Tetanus

Answer 9

Rigid paralysis, infection of wounds with spores of C.tetani
TeNT - single toxin type
Blocks transmission in spinal cord in relaxation pathway

Question 10

Botulism

Answer 10

Flaccid paralysis - intoxication, not an infection (preformed toxin)
8 types: BoNT/A -G + 1
Functions at motor end plate - blocks transmission from neuron to muscle –> no signal to contract

Question 11

Cyrstal structure of BoNT/A

Answer 11

catalytic domain, translocation domain, binding domain

Question 12

BoNT and Tent action

Answer 12

bind to cell surface receptors
bont: internatlised at neuromuscluar junction, escapes endosome, released into neuornal cytoplasm, blocks release of acetylcholine –> flaccid paralysis
Hydrolyses SNARE proteins - bring vesicle to membrane
Tent: stays in endocytotic vesicle and migrates up to spinal cord