title: Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence.
abstract: The function of the Vibrio 7(th) pandemic island-1 (VSP-1) in cholera pathogenesis has remained obscure. Utilizing chromatin immunoprecipitation sequencing and RNA sequencing to map the regulon of the master virulence regulator ToxT, we identify a TCP island-encoded small RNA that reduces the expression of a previously unrecognized VSP-1-encoded transcription factor termed VspR. VspR modulates the expression of several VSP-1 genes including one that encodes a novel class of di-nucleotide cyclase (DncV), which preferentially synthesizes a previously undescribed hybrid cyclic AMP-GMP molecule. We show that DncV is required for efficient intestinal colonization and downregulates V. cholerae chemotaxis, a phenotype previously associated with hyperinfectivity. This pathway couples the actions of previously disparate genomic islands, defines VSP-1 as a pathogenicity island in V. cholerae, and implicates its occurrence in 7(th) pandemic strains as a benefit for host adaptation through the production of a regulatory cyclic di-nucleotide.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Davies
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Bogard
authors.forename: Travis S
authors.initials: TS
authors.lastname: Young
authors.forename: John J
authors.initials: JJ
authors.lastname: Mekalanos
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001483:Base Sequence; D000242:Cyclic AMP / Q000096:biosynthesis*; D015967:Gene Expression Regulation, Viral; D044404:Genomic Islands; D006801:Humans; D007422:Intestines / Q000382:microbiology; D053858:Metabolic Networks and Pathways; D051379:Mice; D008969:Molecular Sequence Data; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D019761:Phosphorus-Oxygen Lyases; D022661:RNA, Untranslated / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D009712:Nucleotides, Cyclic; D022661:RNA, Untranslated; D012367:RNA, Viral; D014157:Transcription Factors; C075626:tcpN protein, Vibrio cholerae; D000242:Cyclic AMP; D019761:Phosphorus-Oxygen Lyases