Bacterial cyclic diguanylate signaling networks sense temperature

Nat Commun. 2021 Mar 31;12(1):1986. doi: 10.1038/s41467-021-22176-2.


Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, we identify a thermosensory diguanylate cyclase (TdcA) that modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogen Pseudomonas aeruginosa. TdcA synthesizes c-di-GMP with catalytic rates that increase more than a hundred-fold over a ten-degree Celsius change. Analyses using protein chimeras indicate that heat-sensing is mediated by a thermosensitive Per-Arnt-SIM (PAS) domain. TdcA homologs are widespread in sequence databases, and a distantly related, heterologously expressed homolog from the Betaproteobacteria order Gallionellales also displayed thermosensitive diguanylate cyclase activity. We propose, therefore, that thermotransduction is a conserved function of c-di-GMP signaling networks, and that thermosensitive catalysis of a second messenger constitutes a mechanism for thermal sensing in bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biofilms / growth & development
  • Chromatography, Liquid
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Gene Expression Regulation, Bacterial
  • Mass Spectrometry
  • Phosphorus-Oxygen Lyases / genetics
  • Phosphorus-Oxygen Lyases / metabolism*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism*
  • Pseudomonas aeruginosa / physiology
  • Second Messenger Systems / physiology*
  • Signal Transduction / physiology*
  • Temperature


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