Hfq-dependent, co-ordinate control of cyclic diguanylate synthesis and catabolism in the plague pathogen Yersinia pestis

Mol Microbiol. 2012 Nov;86(3):661-74. doi: 10.1111/mmi.12011. Epub 2012 Sep 7.


Yersinia pestis, the cause of the disease plague, forms biofilms to enhance flea-to-mammal transmission. Biofilm formation is dependent on exopolysaccharide synthesis and is controlled by the intracellular levels of the second messenger molecule cyclic diguanylate (c-di-GMP), but the mechanisms by which Y. pestis regulates c-di-GMP synthesis and turnover are not fully understood. Here we show that the small RNA chaperone Hfq contributes to the regulation of c-di-GMP levels and biofilm formation by modulating the abundance of both the c-di-GMP phosphodiesterase HmsP and the diguanylate cyclase HmsT. To do so, Hfq co-ordinately promotes hmsP mRNA accumulation while simultaneously decreasing the stability of the hmsT transcript. Hfq-dependent regulation of HmsP occurs at the transcriptional level while the regulation of HmsT is post-transcriptional and is localized to the 5' untranslated region/proximal coding sequence of the hmsT transcript. Decoupling HmsP from Hfq-based regulation is sufficient to overcome the effects of Δhfq on c-di-GMP and biofilm formation. We propose that Y. pestis utilizes Hfq to link c-di-GMP levels to environmental conditions and that the disregulation of c-di-GMP turnover in the absence of Hfq may contribute to the severe attenuation of Y. pestis lacking this RNA chaperone in animal models of plague.

Publication types

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

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / genetics
  • 3',5'-Cyclic-GMP Phosphodiesterases / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / biosynthesis
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial*
  • Host Factor 1 Protein / genetics
  • Host Factor 1 Protein / metabolism*
  • Humans
  • Molecular Sequence Data
  • Phosphorus-Oxygen Lyases / genetics
  • Phosphorus-Oxygen Lyases / metabolism
  • Plague / microbiology*
  • Yersinia pestis / enzymology
  • Yersinia pestis / genetics
  • Yersinia pestis / metabolism*


  • Bacterial Proteins
  • Escherichia coli Proteins
  • Host Factor 1 Protein
  • bis(3',5')-cyclic diguanylic acid
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Phosphorus-Oxygen Lyases
  • diguanylate cyclase
  • Cyclic GMP