Notable bacterial toxins and mechanisms

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Headshot of Joanna Breems, MD, FACP · Clinical Assistant Professor
Joanna Breems
MD, FACP · Clinical Assistant Professor
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These are exemplars of the most notable toxins and their mechanisms. Organisms such as Clostridia perfringens, Staphyloccoccus aureus, and Pseudomonas have a variety of toxins, some of which use similar mechanisms.

Anthrax

A/B toxin with three-protein components. Cell binding component is called protective antigen. There are two enzyme components:

Edema factor
Acts as adenylate cyclase and increases intracellular cAMP, which interferes with intracellular signaling of immune effector cells and disrupts water homeostasis.
Lethal factor
Is metalloprotease that inhibits protein kinases that further disrupts intracellular signaling, eventually leading to apoptosis.

Tetanus

Tetanus is secreted metalloprotease that specifically binds to peripheral neurons and is then transported retrograde to CNS inhibitory neurons. In inhibitory neurons, it cleaves synaptobrevin which is necessary for vesicle fusion and release of GABA. The lack of inhibitory GABA leads to unopposed muscular excitation.

Botulism

Botulism is secreted metalloprotease that binds to peripheral motor neurons where it acts directly on the peripheral nerve, cleaving SNARE proteins that are necessary to vesicle fusion and release of acetylcholine. The lack of acetylcholine at the neuromuscular junction leads to flaccid paralysis of the muscle.

Clostridium difficile

C.diff Toxin A
Enterotoxin that acts as potent neutrophil attractant.
C.diff Toxin B
Cytotoxin factor.
C.diff Binary Toxin
Uncommon; adenosine diphosphate robosyltransferase that disrupts actin cystoskeleton leading to severe clinical disease.

Diphtheria toxin

A/B Toxin. Enzymatic subunit A ADP-ribosyllates host eEF-2. eEf-2 is required for protein synthesis; when inactivated, protein synthesis in the cell shuts down.

Shiga

A/B toxin. B unit binds to glycolipid receptor on epithelial cells. The A unit crosses into the trans-golgi network, then to cytoplasm. It enzymatically modifies the 28S-RNA where acyl tRNA binds. This alteration blocks protein synthesis, leading to cell death.

Cholera

A/B toxin. B subunit binds the toxin to the enterocyte. The A subunit activates adenylate cyclase by adding ADP-ribose to the stimulatory G-protein. The increase in cyclic AMP causes outflow of Cl and H20.

E. coli

Labile toxin
A/B toxin. B unit binds cell membrane. A unit catalyzed ADP-ribosylation of regulatory G-protein, allowing unopposed activity of adenylate cyclase system. In Enterocyte, the result is chloride secretion out of the cell and blockage of NaCl absorption. Heat-labile.
E. coli stable toxin
A/B toxin. A unit catalyzes guanylate cyclase. Increase in cyclic GMP causes net secretion of fluid and electrolytes into bowel lumen.

Pertussis toxin

A/B toxin stimulates adenylate cyclase by adding ADP-ribose to inhibitory G-protein which prevents signal transduction and inhibits normal chemokine receptor action. The result is that lymphocytes do not migrate to tissue and remain in circulation, leading to marked lymphocytosis, a clinical hallmark of pertussis infection.

Clostridia perfringens enterotoxin (Food poisoning)

CPE enterotoxin that is secreted within the GI tract. It disrupts tight junctions between epithelial cells.