Microbial Toxins Flashcards
define microbial toxin
macromolecular products that cause harm by altering cellular structure or function
2 most toxic biological substances
botulinum and tetanus neurotoxins
low doses of LPS–>
macrophages, b cells, alternative complement–> fever, inflammation, acute phase reactants and antibodies
high doses of LPS
DIC and shock
many LPS biological effects are mediated by
cytokines
how do toxins facilitate microbe spread and 3 exaples
break down ECM or degrade necrotic debris- hyaluronidase, collagenase, elastase
hemolysis or cytolysis how do they cause problems
damage cell membrane
pyrogenic exotoxins work ho
stimulate cytokines
3 ex of pyogenic exotoxins
erythrogenic toxins of S progenies and enterotoxins and TSS toxin of s. aureus
what are superantiens
most POTENT t cell activators that work by binding both MHC II on APCs and specific V beta chains on T cells at a site different from antigen binding site to stimulate excessive cytokine production
how does diphtheria toxin and pseudomonas aeruginosa exotoxin A cause problems?
ADP ribotransferases that put a dipthamide on EF2 and inactivate EF2—> inhibit protein synthesis
how does Shiga toxins (shigella dysenteriae) and e coli and ricin plant toxin cause problems
RNA Nglycosidases– remove an adenine from 28S RNA of 60S ribosome–> inhibit protein synthesis
how do heat labile enterotoxins of V. cholera and e coli work?
ADP ribotransferases that activate the ALPHA SUBUNIT OF GS REGULATORY PROTEIN IN CYCLASE COMPLEX–> increase intracellular cAMP in small intestine–> diarrhea
how does pertussis toxin work
ADP ribotransferase that INACTIVATES THE ALPHA SUBUNIT OF Gi REGULATORY PROTEIN to increase intracellular cAMP
bacillus anthraces and bordetella pertussis produce what 2 toxins (respectively)
- anthrax edema factor (EF) and 2. adenylate cyclase toxin
how does anthrax EF and adenylate cyclase toxin work
cause intracellular cAMP to increase
what does anthrax EF and adenylate cyclase require to work
calmodulin and calcium from TARGET CELLS to activate it
antrhax lethal toxin does what
endopeptidase, cleaves many MAP kinase kinase proteins–> inactivates them
clostridium difficile toxins a and b work how
inactivates the Rho family GTPases by transferring glucose from UDP-glucose to the Rho GTPases to alter actin cytoskeleton
2 toxins inhibit neurotransmitter release- what are they and what do they need
botulinum and are zinc dependent endopeptidases
how many antigenic types do you find with botulinum and tetanus toxins
7 and 1 (respectively)
how does botulinum toxin cause problems
inhibit AcH release at myoneural junctions leading to flaccid paralysis of skeletal muscles
which neurotoxin is used therapeutically
botulinum
how does tetanus toxin cause problems
sustained muscular contraction of skeletal muscles by inhibiting release of neurotransmitter from INHIBITORY INTERNEURONS AT SPINAL CORD
both neurtotoxins inactivate what
SNARE proteins needed for neuroexocytosis
3 SNARE proteins
CAMP, Snap 25 and synthaxin
kochs postulates in the version to show that a toxin is implicated in the pathogenesis of an infectious disease
- purified toxin injected –> same symptoms and signs, 2. antitoxin prevents disease 3. virulence correlates with toxin produced 4. nontoxinogenic mutants don’t cause problems and restoring virulence occurs when microbe can produce toxin again
molecular version of koch’s postulates
- phenotype is associated with a species or strain, 2. inactivation of virulence gene–> decreased virulence 3.replace mutant gene with WT restores virulence
microbial toxins that work intracellularly usually enter by
endocytosis
4 things that get into cells and translocate to the right spot in the cell via a translocation domain
diptherai, antrax toxin protective antigen, botulinum, and tetanus
4 toxins that get into the cell and do NOT use a translocation domain (use retrograde pathway from endosomes)
shiga, cholera, e. coli heat labile enterotoxin and pertussus
