Cyclic AMP post-transcriptionally regulates the biosynthesis of a major bacterial autoinducer to modulate the cell density required to activate quorum sensing.

In Vibrio cholerae, expression of the quorum sensing regulator HapR is induced by the accumulation of a major autoinducer synthesized by the activity of CqsA. Here we show that the cAMP-cAMP receptor protein complex regulates cqsA expression at the post-transcriptional level. This conclusion is supported by the analysis of cqsA-lacZ fusions, the ectopic expression of cqsA in Deltacrp mutants and by Northern blot analysis showing that cqsA mRNA is unstable in Deltacrp and Deltacya (adenylate cyclase) mutants. Addition of cAMP to the culture of a Deltacya mutant restored cqsA mRNA stability and cholera autoinducer 1 production. Lowering intracellular cAMP levels by addition of d-glucose increased the cell density required to activate HapR. These results indicate that cAMP acts as a quorum modulator.