bacterial toxins Flashcards

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1
Q

steps required of a bacterium to cause disease

A
  • encounter/enter host
  • establish an infectious niche
  • multiply, cause tissue damage
  • spread to other tissues, or other hosts, or both
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2
Q

factors responsible for pathogenicity

A
  • colonization factors
  • survival factors
  • factors that cuase damage or spread
  • regulatory factors
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3
Q

toxins

A
  • directly damage the host in specific way

- purpose is to obtain cell associated nutrients, facilitate dissemination, and interfere with host defenses

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4
Q

-toxin:

A

protein that damages eukaryotic cells

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5
Q

exotoxin vs endotoxin

A
  • exotoxin: most classical toxins

- endotoxin: non-proteinaceous lipopolysaccharide of gram neg bacteria

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6
Q

classification of toxins

A
  • exotoxins named on the basis of their target

- can classify based on their site of action: target on cell surface, target in cytosol

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7
Q

What questions can you ask when determining the role of a toxin

A
  • toxigenic illnesses were -among the first to be studied
  • investigators can ask: does purified toxin mimic the illnes? do Abs that recognize the toxin decrease the illness? phenotype or specific tox- bacteria
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8
Q

C difficile toxins (gene comp)

A
  • enzymatically active domain
  • cystein protease domain
  • hydrophobic region
  • receptor binding carbohydrates
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9
Q

botulism

A
  • clostridium botilinum
  • obligate anaerobic
  • gram +
  • spore forming
  • toxin causes flaccid paralysis
  • rare
  • intoxication rather than a true infection
  • Abs can alleviate
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10
Q

mechanism of botulism toxin

A
  • A and B toxins
  • A: enzymatically active domain translocated by the B domain. is a protease that prevents Ach release . Cleaves proteins involved in synaptic vescle fusion
  • B: cell binding domain recognizes target cell. receptor mediated endocytosis . acidification results in membrane insertion
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11
Q

targets of botulism

  • A,E
  • C
  • B,D,F,G
A
  • A,E: SNAP-25
  • C: syntaxin
  • D: synaptobrevin
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12
Q

tetanus

A
  • c tetani
  • spore forming obligate anaerobe
  • gram+
  • bacillus
  • spores enter a wound, germinate, and produce toxin
  • similar to the botulism neurotoxin
  • poisons neurotransmitters released by cleavage of proteins involved in vesicle fusion
  • tetanus toxin causes spastci (not flaccid) paralysis
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13
Q

flaccid vs spastic paralysis

A
  • conferred by cell binding specificity of the B subunits
  • tetanus is translocated to the CNS and prevents the release of NTs such as GABA
  • botulism toxins are translocated to the peripheral nerves and prevents the release of stimulatory NTs such as Ach so muscle can not be stimulated to contract
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14
Q

cholera

A
  • large volume of watery diarrhea
  • vibrio cholerae is a gram -, comma shaped, facultative anaerobe
  • noninvasive: all important symptoms are due to action of a single toxin
  • acquired by ingestion of contaminated water or food
  • small intestine is the site of damage induced by toxin
  • generates alkaline pH, which inhibits competing bacteria
  • cholera toxin inducesprofuse watery rice water diarrhea
  • mild to severe cases
  • can result in extreme dehyrdration and hypotension
  • can be rapidly fatal
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15
Q

how is the balance of water controlled in the intestine

A

-ion flux

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16
Q

cholera mechanism

A
  • ADP ribosylation and constitutive activation of a G protein by cholera toxin results in high cAMP which leads to the following
  • decreased Na abosrption, less water absorbed
  • increased Cl secretion, more water secreted
17
Q

cholera

  • toxin model
  • mechanism
  • target
A
  • AB model (A1B5)
  • ADP ribosylation (covalent binding) toxin
  • transfers the ADP ribose group of NAD to eukaryotic protein thereby altering its function
  • target: host cell GTP binding G protein
18
Q

G protein

A
  • act as molecular switches
  • active when bound to GTp and stimulate a signalling cascade
  • inactive when bound to GDP
  • active G proteins will spontaneously turn them selves off by hydrolyzing GTP to GDP
19
Q

mechanism of C diff

A
  • bind the celll
  • endocytosis of toxin
  • acidification of endosome causes the protein to insert itself into the membrane of the endosome via the hydrophobic region
  • now the N term is in the cytosol whicch cleaves and releases the enzymatically active domain
  • active domain does glycosylation of proteins (Rho proteins) resulting in cell death