Endotoxins of Bacteria Flashcards
What are the six general ways bacterial exotoxins assist in the pathogenesis of infectious disease?
- 1) inhibit host cell protein synthesis (causes cell death)
- 2) increase fluid secretion
- 3) inhibit phagocytic ability (promotes survival)
- 4) inhibit release of NTs
- 5) lyse cell membranes (causes cell death)
- 6) shock (these exotoxins are superantigens)
How do endotoxins cause damage?
- (toxic portion of LPS is largely lipid A)
- endotoxins activate:
- IL-1, TNF, and nitric oxide (causes fever and hypotension)
- complement (causes edema and neutrophil chemotaxis)
- tissue factor III AKA thromboplastin (causes DIC)
- note that endotoxins are extremely heat stable, but also require very large doses to cause damage/disease
What are the two mechanisms exotoxins use to inhibit host cell protein synthesis? Which toxins (and organisms) use each?
- 1) inactivate elongation factor (EF-2): diphtheria toxin (Corynebacterium diphtheriae) and exotoxin A (Pseudomonas aeruginosa)
- 2) inactivate the 60S ribosomal subunit: shiga toxin (Shigella spp.) and shiga-like toxin (EHEC)
Which toxins (and organisms) increase fluid secretion?
- heat-labile toxin (LT) and heat-stable toxin (ST) of ETEC
- edema factor of Bacillus anthracis
- cholera toxin of Vibrio cholerae
Which toxins (and organisms) inhibit phagocytic ability?
- pertussis toxin of Bordetella pertussis
Which toxins (and organisms) inhibit NT release? How do these toxins work in general?
- tetanospasmin of Clostridium tetani
- botulinum toxin of Clostridium botulinum
- both are proteases that cleave SNARE proteins (SNARE proteins are required for NT release)
Which toxins (and organisms) lyse cell membranes?
- alpha toxin of Clostridium perfringens
- streptolysin O: Strep. pyogenes
Which toxins are superantigens? How do superantigens work?
- toxic shock syndrome toxin (TSST-1) of Staph. aureus
- exotoxin A of Strep. pyogenes (group A beta-hemolytic Strep)
- superantigens are able to activate any T-cell, resulting in a massive release of cytokines (especially IL-1 and TNF-alpha), resulting in shock
- manifests as toxic shock syndrome: fever, rash, shock
What exotoxin is released by Corynebacterium diphtheriae? How does it work? How does the disease manifest as a result?
- diphtheria toxin
- inhibits protein synthesis by inactivating elongation factor (EF-2) [same mechanism as Pseudomonas’ exotoxin A]
- manifests as pharyngitis and severe lymphadenopathy with grey pseudomembranes in the throat
What exotoxin is released by Pseudomonas aeruginosa? How does it work? How does the disease manifest as a result?
- exotoxin A
- inhibits protein synthesis by inactivating elongation factor (EF-2) [same mechanism as diphtheria toxin]
- manifests just as cell death
What exotoxin is released by Shigella spp.? How does it work? How does the disease manifest as a result?
- shiga toxin (ST)
- inhibits protein synthesis by inactivating the 60S ribosomal subunit [same mechanism as EHEC’s shiga-like toxin]
- manifests as dysentery and hemolytic-uremic syndrome
What exotoxin is released by EHEC? How does it work? How does the disease manifest as a result?
- shiga-like toxin (SLT)
- inhibits protein synthesis by inactivating the 60S ribosomal subunit [same mechanism as Shigella’s shiga toxin]
- manifests as dysentery and hemolytic-uremic syndrome
What exotoxin is released by ETEC? How does it work? How does the disease manifest as a result?
- heat-labile and heat-stable toxins (LT and ST); both increase fluid secretion
- LT over activates adenylate cyclase (raises cAMP) to increase Cl- gut secretion
- ST over activates guanylate cyclase (raises cGMP) to decrease gut NaCl absorption
- both result in excess water in the gut, manifesting as watery diarrhea
What exotoxin is released by Bacillus anthracis? How does it work? How does the disease manifest as a result?
- edema factor
- increases fluid secretion by mimicking adenylate cyclase (raises cAMP) to increase Cl- secretion
- manifests as the edematous borders of the black lesions seen in cutaneous anthrax
What exotoxin is released by Vibrio cholera? How does it work? How does the disease manifest as a result?
- cholera toxin
- increases fluid secretion by permanently ACTIVATING Gs in the gut to increase adenylate cyclase (raises cAMP) to increase Cl- gut secretion
- manifests as severe “rice-water” diarrhea
What exotoxin is released by Bordetella pertussis? How does it work? How does the disease manifest as a result?
- pertussis toxin
- inhibits phagocytic ability by INHIBITING Gi to increase adenylate cyclase (raises cAMP), impairing phagocytosis
- manifests as whooping cough, as the organism is unable to be destroyed by phagocytosis
What exotoxin is released by Clostridium tetani? How does it work? How does the disease manifest as a result? What about Clostridium botulinum?
- C. tetani: tetanospasmin; prevents the release of inhibitory NTs (GABA and glycine), resulting in tetany (spasticity, rises sardonic, and lockjaw)
- C. botulinum: botulinum toxin; prevents the release of ACh at the NMJ, resulting in flaccid paralysis/floppy baby
What exotoxin is released by Clostridium perfringens? How does it work? How does the disease manifest as a result?
- alpha toxin (lecithinase, which is a phospholipase)
- lyses cell membranes by degrading phospholipids
- manifests as myonecrosis and gas gangrene
What exotoxin is released by Strep. pyogenes? How does it work? How does the disease manifest as a result?
- streptolysin O
- lyses cell membranes of RBCs
- ASO (antibodies against streptolysin O) are used to diagnose rheumatic fever
Which exotoxins are A-B toxins? How do these toxins generally function?
- diphtheria toxin, exotoxin A (Pseudomonas), shiga toxin, shiga-like toxin (EHEC); (these all act to inhibit protein synthesis)
- heat-labile toxin only (ETEC), cholera toxin; (these act to increase fluid secretion)
- pertussis toxin (acts to inhibit phagocytic ability)
- A-B toxins have 2 subunits; a B or “binding” subunit and an A or “active” subunit that attaches ADP-ribosyl to disrupt host cell proteins (this is why these toxins are AKA ADP-ribosylating toxins)
