Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence

Cell. 2012 Apr 13;149(2):358-70. doi: 10.1016/j.cell.2012.01.053.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins
  • Base Sequence
  • Cyclic AMP / biosynthesis*
  • Gene Expression Regulation, Viral
  • Genomic Islands
  • Humans
  • Intestines / microbiology
  • Metabolic Networks and Pathways
  • Mice
  • Molecular Sequence Data
  • Nucleotides, Cyclic / metabolism*
  • Phosphorus-Oxygen Lyases
  • RNA, Untranslated / metabolism
  • RNA, Viral / metabolism
  • Sequence Alignment
  • Transcription Factors
  • Vibrio cholerae / genetics
  • Vibrio cholerae / metabolism*
  • Vibrio cholerae / pathogenicity*
  • Virulence

Substances

  • Bacterial Proteins
  • Nucleotides, Cyclic
  • RNA, Untranslated
  • RNA, Viral
  • Transcription Factors
  • tcpN protein, Vibrio cholerae
  • Cyclic AMP
  • Phosphorus-Oxygen Lyases

Associated data

  • GEO/GSE36373