Integration of cyclic di-GMP and quorum sensing in the control of vpsT and aphA in Vibrio cholerae

J Bacteriol. 2011 Nov;193(22):6331-41. doi: 10.1128/JB.05167-11. Epub 2011 Sep 16.


Vibrio cholerae transitions between aquatic environmental reservoirs and infection in the gastrointestinal tracts of human hosts. The second-messenger molecule cyclic di-GMP (c-di-GMP) and quorum sensing (QS) are important signaling systems that enable V. cholerae to alternate between these distinct environments by controlling biofilm formation and virulence factor expression. Here we identify a conserved regulatory mechanism in V. cholerae that integrates c-di-GMP and QS to control the expression of two transcriptional regulators: aphA, an activator of virulence gene expression and an important regulator of the quorum-sensing pathway, and vpsT, a transcriptional activator that induces biofilm formation. Surprisingly, aphA expression was induced by c-di-GMP. Activation of both aphA and vpsT by c-di-GMP requires the transcriptional activator VpsR, which binds to c-di-GMP. The VpsR binding site at each of these promoters overlaps with the binding site of HapR, the master QS regulator at high cell densities. Our results suggest that V. cholerae combines information conveyed by QS and c-di-GMP to appropriately respond and adapt to divergent environments by modulating the expression of key transcriptional regulators.

Publication types

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

MeSH terms

  • Cyclic GMP / metabolism*
  • Gene Expression Regulation, Bacterial*
  • Promoter Regions, Genetic
  • Protein Binding
  • Quorum Sensing*
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Vibrio cholerae / genetics
  • Vibrio cholerae / physiology*


  • AphA protein, Vibrio cholerae
  • Trans-Activators
  • Cyclic GMP