VapBC

VapBC is a widespread toxin–antitoxin system in bacteria and archaea, consisting of VapC, a PIN-domain ribonuclease toxin, and VapB, the neutralizing antitoxin. It is frequently found encoded as a bicistronic operon on plasmids and chromosomes and is named for the two genes vapB and vapC.

In typical VapBC loci, VapB binds VapC to form an inactive complex and also acts as a transcriptional repressor of the operon by recognizing operator sequences. The antitoxin is generally less stable than the toxin and is degraded by proteases under stress, freeing VapC.

VapC toxins cleave RNA to inhibit translation. They are PIN-domain endoribonucleases that require divalent metal ions for activity. While targets vary, many VapC members cleave tRNA or ribosomal RNA precursors, producing growth arrest and often a transition to a dormant state.

Functionally, VapBC systems contribute to plasmid maintenance through post-segregational killing in plasmid-bearing cells, and chromosomal modules are linked to stress tolerance, persistence, and regulation of growth. The balance between VapB and VapC determines cellular outcomes under adverse conditions.

Diversity and distribution: the VapBC family is large, with numerous VapC toxins and VapB antitoxins across bacterial and archaeal species. In pathogenic bacteria such as Mycobacterium tuberculosis, VapBC modules are particularly numerous and studied for roles in adaptation to hostile environments.

Overall, VapBC serves as a model of type II toxin–antitoxin systems, and ongoing research investigates its regulation, targets, and potential as a target for antimicrobial strategies aimed at disrupting persistence and stress responses.