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Rapid Review·Microbiology

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BASIC BACTERIOLOGY

T2High yield

Bacteria with Exotoxins

P130

Focus on

Group the toxins by what they do, and memories how superantigens work.

Key takeaways

Most Exotoxins are AB toxins with two components: B for Binding, which triggers uptake of the Active A component. The A component is usually an ADP-ribosyltransferase. Anthrax is the exception, with three components.

Group them by what the A component actually does

  • Shut down protein synthesis:
    • diphtheria toxin and Pseudomonas exotoxin A both ADP-ribosylate elongation factor EF-2;
    • Shiga and Shiga-like toxin (E. coli O157:H7 which can cause HUS) remove an adenine from the 60S ribosome.
  • Open the fluid taps: cholera, ETEC heat-labile toxin and anthrax edema factor all raise cAMP, while ETEC heat-stable toxin raises cGMP.
  • Blind the phagocyte: pertussis toxin disables Gi, so cAMP rises unopposed.
  • Inhibit release of neurotransmitter: tetanospasmin and botulinum toxin are both SNARE-cleaving proteases, but they cut different neurons.
  • Membrane-lysing toxins: are enzymes that dissolve the host cell.
    • C. perfringens alpha toxin is a phospholipase (lecithinase) that degrades membrane phospholipid directly, producing myonecrosis with gas gangrene and a double zone of hemolysis on blood agar.
    • S. pyogenes streptolysin O lyses red cells, giving beta-hemolysis, and the host antibody response to it is the ASO titre used to document recent infection in rheumatic fever.
  • Superantigens causing shock: SUPERANTIGENS bypass antigen specificity entirely.
    • A normal antigen is processed, loaded into the MHC groove, and activates roughly 0.001% of T cells.
    • A superantigen cross-links the beta region of the TCR to MHC class II OUTSIDE the peptide-binding groove, activating up to 20% of all T cells at once. The result is massive polyclonal release of IL-1, IL-2, IFN-gamma and TNF-alpha, and therefore shock.
    • S. aureus TSST-1 gives toxic shock syndrome; S. pyogenes erythrogenic exotoxin A gives toxic shock-LIKE syndrome and scarlet fever.

The heat-labile versus heat-stable mnemonic for E. coli is worth memorizing

"Labile in the Air (Adenylate cyclase), Stable on the Ground (Guanylate cyclase)".
  • ETEC (enterotoxigenic E. coli) produces two classic toxins: heat-labile toxin (LT) and heat-stable toxin (ST).
  • Heat-labile toxin (LT) is destroyed by heat and acts like cholera toxin: it ADP-ribosylates Gs → activates adenylate cyclase → ↑ cAMP → increased Cl⁻ and water secretion, causing watery diarrhea.
  • Heat-stable toxin (ST) remains active despite heating and activates guanylate cyclase → ↑ cGMP → decreased NaCl absorption and increased fluid secretion, also causing watery diarrhea.
  • Both toxins cause noninflammatory secretory diarrhea, so you generally do not expect fecal leukocytes or
  • Classic NBME association: ETEC causes traveler’s diarrhea, often after contaminated food or water.

ENDOTOXIN

is the LPS of the gram-negative outer membrane, in cocci as well as rods. The three effects of endotoxin
  • It is built from O-antigen plus core polysaccharide plus LIPID A, and lipid A is the toxic part. Neisseria carries a shorter version, lipooligosaccharide (LOS).
  • It reaches the circulation on cell lysis, or from living cells as blebs shed from the outer membrane. Contrast that with an exotoxin, which is actively secreted.
Toxins that INHIBIT PROTEIN SYNTHESIS
BacteriaToxinMechanismManifestation
Corynebacterium diphtheriaeDiphtheria toxinInactivates elongation factor EF-2 by ADP-ribosylationPharyngitis with PSEUDOMEMBRANES and severe lymphadenopathy ("bull neck"), plus myocarditis
Pseudomonas aeruginosaExotoxin AThe same, inactivates EF-2Host cell death
Shigella speciesShiga toxinInactivates the 60S ribosome by REMOVING ADENINE from rRNADamages GI mucosa, producing dysentery
Enterohemorrhagic E. coliShiga-like toxinThe sameToxin-mediated injury and cytokine release, giving HUS (classically O157:H7). Unlike Shigella, EHEC does NOT invade host cells
Toxins that INCREASE FLUID SECRETION
BacteriaToxinMechanismManifestation
Enterotoxigenic E. coliHeat-LABILE toxin (LT)Overactivates ADENYLATE cyclase, raising cAMP, which drives Cl- secretion and water effluxWatery diarrhea. "Labile in the Air, Stable on the Ground"
Enterotoxigenic E. coliHeat-STABLE toxin (ST)Overactivates GUANYLATE cyclase, raising cGMP, which blocks NaCl and water resorptionTraveler's diarrhea
Bacillus anthracisAnthrax toxin (edema factor)IS an adenylate cyclase in its own right, raising cAMPEdematous border around the black eschar of cutaneous anthrax
Vibrio choleraeCholera toxinRaises cAMP by PERMANENTLY ACTIVATING GsVoluminous "RICE-WATER" diarrhea
Toxins that INHIBIT PHAGOCYTIC ABILITY
BacteriaToxinMechanismManifestation
Bordetella pertussisPertussis toxinRaises cAMP by INACTIVATING the inhibitory subunit GiWhooping cough: coughing fits on expiration with a "whoop" on inspiration, the "100-day cough" in adults, and posttussive emesis
Toxins that INHIBIT NEUROTRANSMITTER RELEASE
BacteriaToxinMechanismManifestation
Clostridium tetaniTetanospasminProtease that cleaves SNARE, which vesicle fusion requiresBlocks INHIBITORY GABA and glycine release from RENSHAW cells, giving SPASTIC paralysis, risus sardonicus, trismus and opisthotonos
Clostridium botulinumBotulinum toxinThe same, cleaves SNAREBlocks ACh release at the NMJ, giving FLACCID paralysis. Infant botulism follows ingestion of SPORES (soil, raw honey), foodborne botulism follows ingestion of PREFORMED TOXIN (home-canned food)
Toxins that LYSE CELL MEMBRANES
BacteriaToxinMechanismManifestation
Clostridium perfringensAlpha toxinPhospholipase (LECITHINASE) that degrades tissue and cell membranesPhospholipid degradation gives MYONECROSIS ("gas gangrene") and hemolysis, with a "DOUBLE ZONE" of hemolysis on blood agar
Streptococcus pyogenesStreptolysin OProtein that degrades the cell membraneLyses RBCs, giving beta-hemolysis. The host antibody (ASO titre) documents recent infection in RHEUMATIC FEVER, and must not be confused with the immune complexes of PSGN
SUPERANTIGENS causing shock
BacteriaToxinMechanismManifestation
Staphylococcus aureusTSST-1Cross-links the beta region of the TCR to MHC class II on APCs OUTSIDE the antigen-binding site, releasing IL-1, IL-2, IFN-gamma and TNF-alpha in bulkToxic shock syndrome with fever, rash and shock. Its other toxins cause scalded skin syndrome (exfoliative toxin) and food poisoning (heat-stable enterotoxin)
Streptococcus pyogenesErythrogenic exotoxin AThe same superantigen mechanismToxic shock-LIKE syndrome with fever, rash and shock, plus scarlet fever

How it's tested

The cAMP convergence is the elegant question. Cholera toxin, ETEC heat-labile toxin, anthrax edema factor and pertussis toxin all raise cAMP by four DIFFERENT mechanisms: cholera permanently activates Gs, pertussis inactivates Gi, anthrax edema factor is itself an adenylate cyclase, and LT overactivates the host enzyme. Same endpoint, four routes, and the stem will name only one of them.

The other guaranteed contrast is tetanus against botulism. Both toxins are SNARE-cleaving proteases, yet they produce opposite paralysis, because tetanus blocks the INHIBITORY neurotransmitters (spastic) while botulinum blocks EXCITATORY ACh (flaccid).

Diphtheria and Pseudomonas exotoxin A share a target too: both ADP-ribosylate EF-2, so a question that describes halted translation with no ribosomal damage is pointing at one of those two.

The superantigen mechanism is the highest-yield immunology and micro crossover. TSST-1 bridges MHC II to the TCR beta chain outside the peptide-binding groove, so it activates up to 20% of all T cells nonspecifically instead of the roughly 0.001% a conventional antigen reaches. The polyclonal cytokine release is what produces shock, and no specific antigen is ever involved.

The clinical discriminator between the two superantigen syndromes is reliable. Staphylococcal TSS is tied to tampons or nasal packing and the culture is often NEGATIVE, because the toxin travelled and the organism stayed put. Streptococcal toxic shock-like syndrome accompanies a painful skin infection such as necrotizing fasciitis, and blood cultures are usually POSITIVE.

The C. perfringens stem is visual: crepitus in a contaminated wound with a double zone of hemolysis on culture points at alpha toxin, a lecithinase, and the answer is surgical debridement rather than antibiotics alone.

Go deeper

First Aid "Bacteria with exotoxins"; SketchyMicro. Anchor ADP-ribosylation of EF-2 (diphtheria and Pseudomonas exotoxin A), 60S inactivation by Shiga and Shiga-like toxin leading to HUS, the four routes to raised cAMP, and the two SNARE-cleaving neurotoxins.

High-yield images1
Endotoxin (lipid A of gram-negative LPS) effects: macrophage activation via TLR4/CD14 (IL-1/IL-6 -> fever, TNF-alpha -> fever + hypotension, nitric oxide -> hypotension), complement activation (C3a/C5a -> histamine release and neutrophil chemotaxis), and tissue factor activation (-> DIC).

Flashcards for this page

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Low activity of which neurotransmitters results in the spastic paralysis, risus sardonicus, trismus, and opisthotonos caused by tetanospasmin?

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