c-di-GMP modulates type IV MSHA pilus retraction and surface attachment in Vibrio cholerae

Nat Commun. 2020 Mar 25;11(1):1549. doi: 10.1038/s41467-020-15331-8.


Biofilm formation by Vibrio cholerae facilitates environmental persistence, and hyperinfectivity within the host. Biofilm formation is regulated by 3',5'-cyclic diguanylate (c-di-GMP) and requires production of the type IV mannose-sensitive hemagglutinin (MSHA) pilus. Here, we show that the MSHA pilus is a dynamic extendable and retractable system, and its activity is directly controlled by c-di-GMP. The interaction between c-di-GMP and the ATPase MshE promotes pilus extension, whereas low levels of c-di-GMP correlate with enhanced retraction. Loss of retraction facilitated by the ATPase PilT increases near-surface roaming motility, and impairs initial surface attachment. However, prolonged retraction upon surface attachment results in reduced MSHA-mediated surface anchoring and increased levels of detachment. Our results indicate that c-di-GMP directly controls MshE activity, thus regulating MSHA pilus extension and retraction dynamics, and modulating V. cholerae surface attachment and colonization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Bacterial Adhesion
  • Biofilms / growth & development
  • Cell Tracking
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism
  • Fimbriae, Bacterial / genetics
  • Fimbriae, Bacterial / metabolism*
  • Movement
  • Vibrio cholerae / cytology
  • Vibrio cholerae / metabolism
  • Vibrio cholerae / physiology*


  • Fimbriae Proteins
  • bis(3',5')-cyclic diguanylic acid
  • Adenosine Triphosphatases
  • Cyclic GMP