Cyclic di-GMP signalling controls virulence properties of Salmonella enterica serovar Typhimurium at the mucosal lining

Environ Microbiol. 2010 Jan;12(1):40-53. doi: 10.1111/j.1462-2920.2009.02032.x. Epub 2009 Aug 18.


Cyclic di-GMP (c-di-GMP), a novel secondary signalling molecule present in most bacteria, controls transition between motility and sessility. In Salmonella enterica serovar Typhimurium (S. typhimurium) high c-di-GMP concentrations favour the expression of a biofilm state through expression of the master regulator CsgD. In this work, we investigate the effect of c-di-GMP signalling on virulence phenotypes of S. typhimurium. After saturation of the cell with c-di-GMP by overexpression of a di-guanylate cyclase, we studied invasion and induction of a pro-inflammatory cytokine in epithelial cells, basic phenotypes that are major determinants of S. typhimurium virulence. Elevated c-di-GMP had a profound effect on invasion into and IL-8 production by the gastrointestinal epithelial cell line HT-29. Invasion was mainly inhibited through CsgD and the extracellular matrix component cellulose, while inhibition of the pro-inflammatory response occurred through CsgD, which inhibited the secretion of monomeric flagellin. Our results suggest that transition between biofilm formation and virulence in S. typhimurium at the epithelial cell lining is mediated by c-di-GMP signalling through CsgD and cellulose expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Adhesion
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biofilms
  • Cell Line
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology*
  • Female
  • Flagellin / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Bacterial
  • Humans
  • Interleukin-8 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Salmonella Infections, Animal / microbiology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / pathogenicity*
  • Signal Transduction
  • Virulence*


  • Bacterial Proteins
  • Interleukin-8
  • Flagellin
  • bis(3',5')-cyclic diguanylic acid
  • Cyclic GMP