Figure 8.

Model explain transcriptional regulation of the kacAT operon by conditional cooperativity. (A) At [A] > [T], antitoxin KacA binds weakly to kacAT operator DNA, resulting in modest transcriptional repression. (B) At an [A]:[T] ratio close to 1:2, KacT and KacA form a stable heterohexameric complex that binds strongly to operator DNA, resulting in efficient repression. (C) At [T] > [A], the excess of KacT destabilizes operator binding, resulting in de-repression of transcription, replenishment of KacA antitoxin. This complicated mode of transcriptional regulation by the T:A ratio secures replenishment of antitoxin during states of high toxin levels and thus, slow growth. Thus, this mechanism may reduce fortuitous activation of toxin and may also allow for the resuscitation of persister cells as well as promote restart of cell growth after the termination of stressful conditions (21).