Bacterial Toxins and Exotoxins

Exotoxins are proteins secreted by bacteria that damage host cells, often at sites distant from the infecting organism and at extremely low concentrations. Among the most potent biological poisons known, they account for much of the specific tissue injury in diseases such as diphtheria, cholera, tetanus, and botulism, and they have shaped both the understanding of pathogenesis and the development of vaccines.

Definition

An exotoxin is a soluble protein secreted (or released) by bacteria that acts on host cells to cause damage; many are AB toxins, in which a binding (B) component delivers an enzymatically active (A) component into the target cell.

Scope

This topic covers the major structural and functional classes of bacterial protein toxins, the AB (binding-and-active) architecture shared by many of them, their principal modes of action on host cells, and their relationship to disease and to toxoid vaccines. It is a reference topic; it does not address clinical management of any intoxication.

Core questions

• How are bacterial protein toxins structured, and how does the AB design separate binding from activity?
• By what enzymatic or membrane mechanisms do exotoxins damage host cells?
• How do exotoxins relate to specific diseases and to toxoid-based vaccines?

Key concepts

• Exotoxin versus endotoxin
• AB toxin architecture
• ADP-ribosylating toxins (e.g. diphtheria, cholera, pertussis)
• Pore-forming toxins
• Neurotoxins (tetanus, botulinum)
• Superantigens
• Toxoid vaccines

Mechanisms

Many exotoxins share an AB organization: a B moiety binds a host-cell receptor and mediates entry, while an A moiety carries enzymatic activity into the cytosol. Common A-domain activities include ADP-ribosylation of host targets (diphtheria toxin inactivates elongation factor 2 to halt protein synthesis; cholera toxin modifies a G protein to dysregulate cyclic AMP), proteolysis of neuronal SNARE proteins by tetanus and botulinum neurotoxins, and other covalent modifications. A separate class, the pore-forming toxins, inserts into host membranes to disrupt their integrity, and superantigens act by cross-linking MHC and T-cell receptors to trigger massive cytokine release. Because the active site drives toxicity, chemically inactivated toxins (toxoids) retain immunogenicity and form the basis of several vaccines.

Clinical relevance

Exotoxins explain the specific signs of several classic bacterial diseases and are the antigenic basis of toxoid vaccines such as those against diphtheria and tetanus. This entry summarizes toxin biology for reference and is not a guide to diagnosing or treating intoxication.

History

Bacterial toxins were among the first virulence factors identified: late nineteenth-century work on diphtheria and tetanus toxins led directly to antitoxins and to the toxoid vaccines of the early twentieth century. Later molecular studies resolved the AB architecture and the enzymatic activities that define the major toxin families, linking specific biochemical lesions to disease.

Key figures

• Alison D. O'Brien
• R. John Collier
• Joseph T. Barbieri

Seminal works

• schmitt-1999
• henkel-2010

Frequently asked questions

What is the difference between an exotoxin and an endotoxin?

An exotoxin is a secreted protein with specific, often enzymatic activity that can act far from the bacterium, whereas endotoxin is the lipopolysaccharide of the Gram-negative outer membrane, released mainly on cell lysis, that triggers generalized inflammation.

What is a toxoid?

A toxoid is a bacterial toxin that has been chemically inactivated so that it no longer causes damage but still provokes a protective antibody response, which is the principle behind the diphtheria and tetanus vaccines.