Exotoxin Overview Exotoxins are proteinsreleased by both Gram-positive and Gram-negative bacteria certain Gram-positive and Gram-negative bacteria produce exotoxins exotoxins are not heat stable destroyed rapidly at 60°C except Staphylococcal enterotoxin Exotoxin types and examples of each enterotoxins act on the GI tract to cause diarrhea cause osmotic pull of fluid into the intestines 2 mechanisms by which enterotoxins cause disease infectious diarrhea bacteria colonize GI tract and continuously secrete enterotoxin diarrhea continues until infection is cleared examples Vibrio cholera E. coli Campylobacter jejuni Shigella dysenteriae food poisoning bacteria grow in food and release enterotoxin into food less than 24 hours of diarrhea and vomiting examples Bacillus cereus Staphylococcus aureus neurotoxins act on the nerves or NMJ to cause paralysis Clostridium tetani pyrogenic exotoxins stimulate release of cytokines cause rash, fever, toxic shock syndrome S. aureus, Streptococcus pyogenes tissue invasive exotoxins enzymes that destroy tissue to allow bacteria to invade the host "SHiN" bacteria group A streptococcus cAMP inducers V. cholerae, Bordetella pertussis, and E. coli (ETEC) via ADP ribosylation Bacillus anthracis edema factor is an adenylate cyclase A-B ADP ribosylation Corynebacterium diphtheriae and Pseudomonas Vibrio cholerae E. coli Bordetella pertussis S. aureus secretes multiple types of exotoxins as described below superantigen TSST-1 enterotoxin exfoliatin protein A Enterotoxins V. cholerae toxin AB toxin A subunit is active ADP ribosylation of G protein stimulates adenylyl cyclase permanently activates Gs ↑ pumping of Cl- into gut and ↓ Na+ absorption H2O moves into gut lumen causes voluminous rice-water diarrhea "turns the 'on' on" E. coli (ETEC) heat-labile toxin stimulates adenylate cyclase → ↑ cAMP increase Cl- secretion and H2O efflux just like cholera heat-stable toxin stimulates guanylate cyclase → ↑ cGMP decrease resorption of NaCl and H2O both cause watery diarrhea "Labile like the Air, stable like the Ground" Neurotoxins C. tetani blocks the release of inhibitory neurotransmitters GABA and glycine from Renshaw cells in the spinal cord causes opisthotonus, trismus (lockjaw), and risus sardonicus zinc-dependent protease C. botulinum blocks the presynaptic release of acetylcholine at the NMJ causes anticholinergic symptoms, CNS paralysis (especially cranial nerves) spores found in honey (causes floppy baby) improperly canned food contains preformed toxin (effects adults) zinc-dependent protease Pyrogenic exotoxins S. aureus TSST-1 superantigen causes toxic shock syndrome (fever, rash, shock) binds directly to MHC II and T cell receptor simultaneously, activating large numbers of T cells to stimulate release of IFN-γ, IL-2, IL-1 additionally, S. aureus secretes enterotoxins cause food poisoning exfoliatin causes staphylococcal scalded skin syndrome protein A binds Fc region of Ig prevents opsonization and phagocytosis S. pyogenes scarlet fever-erythrogenic toxin causes toxic shock-like syndrome streptolysin O is a hemolysin antigen for ASO antibody used in the diagnosis of rheumatic fever Tissue invasive exotoxins S. pneumoniae, Haemophilus influenza type B, and Neisseria all secrete IgA protease in order to colonize respiratory mucosa enzyme that cleaves IgA recall that these 3 bacteria are the "SHiN" encapsulated bacteria Group A streptococcus M protein helps prevent phagocytosis Miscellaneous exotoxins Shiga toxin inactivates mammalian 60S ribosomal subunit prevents binding of tRNA to 60S subunit Shiga toxin released by Shigella Shiga-like toxin (similar mechanism) released by EHEC active A subunit + 5 binding B subunits plasmid transmitted to E. coli by temperate bacteriophage B. pertussis AB toxin increases cAMP by inhibiting Gαi causes whooping cough "turns the 'off' off" inhibits chemokine receptor, causing lymphocytosis impairs phagocytosis by host B. anthracis toxin induces edema factor, a bacterial adenylate cyclase (↑ cAMP) Corynebacterium diphtheriae AB toxin B subunit binds cardiac and neural cells A subunit inactivates elongation factor 2 (EF-2) → inhibit host cell protein synthesis → death via ADP ribosylation EF-2 is needed for peptide chain translocation on the ribosome during translation also seen with Pseudomonas exotoxin A causes pharyngitis and "pseudomembrane" in throat C. difficile A-B cytotoxin kills enterocytes and causes pseudomembranous colitis toxin A attracts neutrophils, causing inflammation causes loss of water into gut lumen toxin B actin depolymerization loss of cytoskeleton integrity C. perfringens α toxin (also known as phospholipase C or lecithinase) causes gas gangrene get double zone of hemolysis on blood agar degrades lecithin, a component of cell phospholipid membranes causes loss of cell membrane integrity leads to membrane destruction, cell death, necrosis, hemolysis