A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation

A new autoinducer–receptor pair, 3,5-dimethylpyrazin-2-ol (DPO)–VqmA, acts in parallel to canonical Vibrio cholerae quorum-sensing pathways. Downstream of VqmA is the small RNA target VqmR, which, like DPO, represses genes required for biofilm formation and toxin production. Quorum sensing (QS) is a cell–cell communication process that enables bacteria to track cell population density and orchestrate collective behaviors. QS relies on the production and detection of, and the response to, extracellular signal molecules called autoinducers. In Vibrio cholerae , multiple QS circuits control pathogenesis and biofilm formation. Here, we identify and characterize a new QS autoinducer–receptor pair. The autoinducer is 3,5-dimethylpyrazin-2-ol (DPO). DPO is made from threonine and alanine, and its synthesis depends on threonine dehydrogenase (Tdh). DPO binds to and activates a transcription factor, VqmA. The VqmA–DPO complex activates expression of vqmR , which encodes a small regulatory RNA. VqmR represses genes required for biofilm formation and toxin production. We propose that DPO allows V. cholerae to regulate collective behaviors to, among other possible roles, diversify its QS output during colonization of the human host.