Cyclic diguanylate signaling in Gram-positive bacteria

FEMS Microbiol Rev. 2016 Sep;40(5):753-73. doi: 10.1093/femsre/fuw013. Epub 2016 Jun 26.


The nucleotide second messenger 3'-5' cyclic diguanylate monophosphate (c-di-GMP) is a central regulator of the transition between motile and non-motile lifestyles in bacteria, favoring sessility. Most research investigating the functions of c-di-GMP has focused on Gram-negative species, especially pathogens. Recent work in Gram-positive species has revealed that c-di-GMP plays similar roles in Gram-positives, though the precise targets and mechanisms of regulation may differ. The majority of bacterial life exists in a surface-associated state, with motility allowing bacteria to disseminate and colonize new environments. c-di-GMP signaling regulates flagellum biosynthesis and production of adherence factors and appears to be a primary mechanism by which bacteria sense and respond to surfaces. Ultimately, c-di-GMP influences the ability of a bacterium to alter its transcriptional program, physiology and behavior upon surface contact. This review discusses how bacteria are able to sense a surface via flagella and type IV pili, and the role of c-di-GMP in regulating the response to surfaces, with emphasis on studies of Gram-positive bacteria.

Keywords: Gram-positive; adherence; biofilm; cyclic diguanylate; motility; signaling.

Publication types

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

MeSH terms

  • Bacterial Adhesion / physiology*
  • Biofilms / growth & development
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Fimbriae, Bacterial / metabolism*
  • Flagella / metabolism*
  • Gram-Positive Bacteria / metabolism*
  • Microbial Interactions / physiology
  • Signal Transduction


  • bis(3',5')-cyclic diguanylic acid
  • Cyclic GMP