Bacteria use quorum sensing to monitor cell density and coordinate group behaviours. In Vibrio cholerae, the causative agent of the diarrheal disease cholera, quorum sensing is connected to biofilm formation and virulence gene expression via the two autoinducer molecules, AI-2 and CAI-1. Recently, we discovered another QS system operating in V. cholerae. This system operates independent of the CAI-1 and AI-2-controlled QS pathway and relies on the catabolic degradation of L-threonine by threonine dehydrogenase (encoded by tdh) and the concomitant synthesis of another autoinducer, called DPO (3,5-dimethylpyrazin-2-ol). DPO is sensed by VqmA, a cytoplasmic LuxR-type transcriptional regulator, which induces the transcription of the VqmR sRNA. VqmR belongs to the ubiquitous class of Hfq-associated regulatory RNAs and inhibits multiple trans-encoded target genes through direct base-pairing with their respective mRNAs. The target spectrum of VqmR also includes the transcripts encoding VpsT and AphA, key activators of biofilm formation and virulence gene expression, respectively. Consequently, DPO inhibits biofilm formation and the transcription of virulence gene in V. cholerae. We further show that DPO acts in concert with the AI-2 and CAI-1 autoinducers to globally control gene expression in V. choleraeand that all three autoinducers are required to promote a full quorum sensing response.

Selected recent publications

1. Herzog R., et al., (2019) Three autoinducer molecules act in concert to control virulence gene expression in Vibrio cholerae. Nucleic Acid Res.47:3171-3183.

2. Papenfort K., et al., (2017) A Vibrio cholerae autoinducer-receptor pair that controls biofilm formation. Nat. Chem. Biol.13:551-557.

3. Papenfort K. and Bassler B.L. (2016) Quorum sensing signal-response systems in Gram-negative bacteria. Nat. Rev. Microbiol. 14:576-588.

4. Feng L., Rutherford, S.T., Papenfort K., et al., (2015) A qrrnoncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics. Cell 160:228-24