bacterial toxins Flashcards
steps required of a bacterium to cause disease
- encounter/enter host
- establish an infectious niche
- multiply, cause tissue damage
- spread to other tissues, or other hosts, or both
factors responsible for pathogenicity
- colonization factors
- survival factors
- factors that cuase damage or spread
- regulatory factors
toxins
- directly damage the host in specific way
- purpose is to obtain cell associated nutrients, facilitate dissemination, and interfere with host defenses
-toxin:
protein that damages eukaryotic cells
exotoxin vs endotoxin
- exotoxin: most classical toxins
- endotoxin: non-proteinaceous lipopolysaccharide of gram neg bacteria
classification of toxins
- exotoxins named on the basis of their target
- can classify based on their site of action: target on cell surface, target in cytosol
What questions can you ask when determining the role of a toxin
- 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
C difficile toxins (gene comp)
- enzymatically active domain
- cystein protease domain
- hydrophobic region
- receptor binding carbohydrates
botulism
- clostridium botilinum
- obligate anaerobic
- gram +
- spore forming
- toxin causes flaccid paralysis
- rare
- intoxication rather than a true infection
- Abs can alleviate
mechanism of botulism toxin
- 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
targets of botulism
- A,E
- C
- B,D,F,G
- A,E: SNAP-25
- C: syntaxin
- D: synaptobrevin
tetanus
- 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
flaccid vs spastic paralysis
- 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
cholera
- 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
how is the balance of water controlled in the intestine
-ion flux
cholera mechanism
- 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
cholera
- toxin model
- mechanism
- target
- 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
G protein
- 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
mechanism of C diff
- 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