Remy Loris

The parDE family of toxin-antitoxin (TA) operons is ubiquitous in bacterial genomes and, in Vibrio cholerae , is an essential component to maintain the presence of chromosome II. Here, we show that transcription of the V. cholerae parDE2 (Vc parDE ) operon is regulated in a toxin:antitoxin ratio–dependent manner using a molecular mechanism distinct from other type II TA systems. The repressor of the operon is identified as an assembly with a 6:2 stoichiometry with three interacting ParD2 dimers bridged by two ParE2 monomers. This assembly docks to a three-site operator containing 5′- GGTA-3′ motifs. Saturation of this TA complex with ParE2 toxin results in disruption of the interface between ParD2 dimers and the formation of a TA complex of 2:2 stoichiometry. The latter is operator binding–incompetent as it is incompatible with the required spacing of the ParD2 dimers on the operator.