A 3'UTR-derived small RNA modulates the life-cycle of the cholera toxin-encoding filamentous phage, CTX? [RNA-Seq]

Bacteriophages (phages) are well known to be one of the major driving forces in bacterial evolution. This is also true for virulent microorganisms, such as the major human pathogen Vibrio cholerae, whose pathogenic potential and epidemic proliferation largely depends on the interaction with environmental phages. Specifically, integration of the CTX? phage genome into the first chromosome of V. cholerae also involved the ctxAB genes, encoding the principle toxin responsible for the severe acute diarrheal disease, cholera. Whereas the mechanisms underlying CTX?-associated horizontal gene transfer and control of the ctxAB genes have been intensively studied over the past years, post-transcriptional regulation affecting the CTX? lifecycle has not been documented. Here, we report the discovery and characterization of the CisR small RNA (sRNA) that is produced from the 3'UTR (untranslated region) of the prtV gene and inhibits the expression of the CTX?-encoded cep mRNA. CisR-mediated repression of cep involves Hfq-assisted base-pairing of the two transcripts and results in reduced CTX? production under stress conditions. We further show that transcription of prtV-cisR requires both, the master quorum sensing transcription factor HapR, as well CRP, which coordinates global carbon metabolism. Taken together, our work provides evidence that V. cholerae employs sRNA-mediated post-transcriptional gene regulation to coordinate CTX? activation with both cell density and nutrient availability. Overall design: RNA-seq expression profiling of Vibrio cholerae strain KPS14 WT grown in LB or AKI medium