Toxins

Toxins


Table Of Contents

Toxins Summary

OrganismToxins
Bacillus AnthracisEdema Toxin (Edema Factor)
– Mimics AC to increase cAMP
– Probably causes edematous borders of black eschar in cutaneous anthrax
Bordetella PertussisPertussis Toxin
– Overactivates AC to increase cAMP by DISABLING Gi (disabled Gi)
– Stops phagocytosis
– Causes Whooping Cough
Clostridium BotulinumBotulinum Toxin
– Proteases that cleave SNARE (soluble NSF attachment protein receptor)
– Flaccid paralysis, floppy baby, prevents the release of excitatory ACh at NMJ
– Flaccid paralysis
Clostridium PerfringensAlpha Toxin
– Lecithinase that degrades tissue/cell membranes
– Gas gangrene
– Double zone of hemolysis
Clostridium TetaniTetanospasmin
– Proteases that cleave SNARE (soluble NSF attachment protein receptor)
– Spastic paralysis, risus sardonicus, lockjaw,
– Can’t release inhibitory GABA/Glycine from Renshaw cells in SC
Corynebacterium DiphtheriaeDiphtheria toxin
– Inactivates EF-2 (ribosylation)
– Causes pharyngitis w/ pseudomembranes and severe LAD (bull’s neck)
EHECShiga-like toxin
– Inactivate 60S ribosome by removing As from rRNA
– Enhance cytokine release causing HUS
– Serotype O157:H7
– DOES NOT INVADE HOST CELLS
ETECHeat-Labile Toxin
– Overactivates AC to raise cAMP –> increase Cl-/H2O secretion in the gut

Heat-Stable Toxin
– Overactivates HC to raise cGMP –> decrease resorption of NaCl and H2O in gut
Pseudomonas AeruginosaExotoxin A
– Inactivates EF-2 (ribosylation
– Causes host cell death
Shigella speciesShiga Toxin
– Inactivate 60S ribosome by removing As from rRNA
– Causes GI mucosal damage –> dysentery
– Increases cytokine release –> HUS
Staphylococcus AureusTSST-1
– Binds to MHC II/TCR outside Ag binding site to cause an overwhelming release of IL-1/2, IFN-Gamma, and

TNF-Alpha
– TSS
– SSS = exfoliative toxin
– Food poisoning = pre-formed enterotoxin
Streptococcus PyogenesStreptolysin O
– Protein that degrades cell membrane
– Lyses RBCs, Beta-hemolysis, host Abs made, diagnose RF

Exotoxin A
– Binds to MHC II/TCR outside Ag binding site to cause an overwhelming release of IL-1/2, IFN-Gamma, and TNF-Alpha
– Leads to Toxic Shock Syndrome
Vibrio CholeraeCholera Toxin
– Overactivates AC to increase cAMP via Gs
– Increased Cl- secretion into the gut and H2O efflux
– Massive rice-water diarrhea

Endotoxin

  • LPS found in Gram- outer membranes
  • O antigen + Core polysaccharide + Lipid A (toxic component)
  • Released upon cell lysis or by blebbing off of living cells (NOT exotoxin)
  • Effects:
    • – Macrophage activation (TLR4)
    • – Complement activation
    • – Tissue factor activation
  • ENDOTOXINS:
    • – Edema
    • – NO
    • – DIC/Death
    • – Outer membrane
    • – TNF-Alpha
    • – O-Ag + core poly + lipid A
    • – eXtremely heat stable
    • – IL-1/6
    • – Neutrophil chemotaxis
    • – Shock

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