Regulation of c-di-GMP metabolism in biofilms

Future Microbiol. 2009 Apr;4(3):341-58. doi: 10.2217/fmb.09.7.


Cyclic (5 to 3 )-diguanosine monophosphate (c-di-GMP) is a small molecule that regulates the transition between the sessile and motile lifestyle, an integrative part of biofilm formation and other multicellular behavior, in many bacteria. The recognition of c-di-GMP as a novel secondary messenger soon raised the question about the specificity of the signaling system, as individual bacterial genomes frequently encode numerous c-di-GMP metabolizing proteins. Recent work has demonstrated that several global regulators concertedly modify the expression of selected panels of c-di-GMP metabolizing proteins, which act on targets with physiological functions. Within complex feed-forward arrangements, the global regulators commonly combine the control of c-di-GMP metabolism with the direct regulation of proteins with functions in motility or biofilm formation, leading to precise and fine-tuned output responses that determine bacterial behavior. c-di-GMP metabolizing proteins are also controlled at the post-translational level by mechanisms including phosphorylation, localization, protein-protein interactions or protein stability. A detailed understanding of such complex regulatory mechanisms will not only help to explain the specificity in c-di-GMP signaling systems, but will also be necessary to understand the high phenotypic diversity within bacterial biofilms at the single cell level.

Publication types

  • Review

MeSH terms

  • Biofilms*
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Enzyme Activation
  • Enzymes / metabolism
  • Flagella / metabolism
  • Gene Expression Regulation, Bacterial
  • Gene Expression Regulation, Enzymologic
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Quorum Sensing
  • RNA Processing, Post-Transcriptional
  • RNA Stability
  • Second Messenger Systems


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