Functional characterization of core components of the Bacillus subtilis cyclic-di-GMP signaling pathway

J Bacteriol. 2013 Nov;195(21):4782-92. doi: 10.1128/JB.00373-13. Epub 2013 Jul 26.

Abstract

Bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger that regulates adaptation processes, including biofilm formation, motility, and virulence in Gram-negative bacteria. In this study, we have characterized the core components of a c-di-GMP signaling pathway in the model Gram-positive bacterium Bacillus subtilis. Specifically, we have directly identified and characterized three active diguanylate cyclases, DgcP, DgcK, and DgcW (formerly YtrP, YhcK, and YkoW, respectively), one active c-di-GMP phosphodiesterase, PdeH (formerly YuxH), and a cyclic-diguanylate (c-di-GMP) receptor, DgrA (formerly YpfA). Furthermore, elevation of c-di-GMP levels in B. subtilis led to inhibition of swarming motility, whereas biofilm formation was unaffected. Our work establishes paradigms for Gram-positive c-di-GMP signaling, and we have shown that the concise signaling system identified in B. subtilis serves as a powerful heterologous host for the study of c-di-GMP enzymes from bacteria predicted to possess larger, more-complex signaling systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cloning, Molecular
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Bacterial / physiology*
  • Molecular Structure
  • Protein Binding
  • Signal Transduction

Substances

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