holotoxin

Holotoxin is a term used to describe the complete, functional toxin molecule produced by certain bacteria, comprising both the enzymatic A subunit and the binding/translocation B subunit (or subunits) in AB toxins. The holotoxin can be a single polypeptide that is proteolytically processed into A and B components, often linked by a disulfide bond, or an oligomeric assembly such as AB5, where a single A subunit is associated with a pentamer of B subunits. The holotoxin designation distinguishes the intact toxin from isolated subunits or fragments.

Mechanism of action typically involves two coordinated steps. The B component binds to specific receptors on the surface of target cells and mediates entry via endocytosis. Acidification within the endosome or other conformational changes enable translocation of the A subunit into the cytosol, where the A subunit exerts its enzymatic activity, disrupting essential cellular processes and causing toxicity.

Examples of holotoxins include botulinum neurotoxin and tetanus toxin (both AB toxins with B components that target neural tissue), cholera toxin and diphtheria toxin (AB toxins with distinct modes of action), and shiga toxin (an AB5 toxin). In each case, the holotoxin refers to the complete toxin complex capable of binding, cellular entry, and enzymatic effect, as opposed to individual subunits.

Safety and research relevance: holotoxins are among the most potent natural toxins and are handled under strict biosafety conditions. Research often uses non-toxic derivatives or inactive mutants to study structure–function relationships, receptor interactions, and potential countermeasures such as vaccines and antitoxins.