Regulatory small RNAs circumvent the conventional quorum sensing pathway in pandemic Vibrio cholerae

Using a process called quorum sensing (QS), bacteria communicate with extracellular signal molecules called autoinducers (AIs). Response to AIs allows bacteria to coordinate gene expression on a population-wide scale and thereby carry out particular behaviors in unison, much like multicellular organisms. In Vibrio cholerae El Tor, the etiological agent of the current cholera pandemic, AI information is transduced internally through a phosphorelay circuit that impinges on the transcription of multiple small regulatory RNAs (sRNAs). These RNAs base-pair with, and repress the translation of, the mRNA encoding the master transcriptional regulator HapR. In V. cholerae, HapR controls virulence factor expression and biofilm formation. Here we identify a sRNA-dependent, HapR-independent QS pathway in which the sRNAs base-pair with a new target mRNA and activate translation by preventing formation of a translation-inhibiting stem-loop structure. We show that the classical V. cholerae strain, which caused previous pandemics and is reportedly incapable of QS because of a nonfunctional HapR, nonetheless exhibits QS-controlled gene expression through this new HapR-independent pathway.