A matter of life and death: cell wall homeostasis and the WalKR (YycGF) essential signal transduction pathway

Mol Microbiol. 2008 Dec;70(6):1307-22. doi: 10.1111/j.1365-2958.2008.06483.x. Epub 2008 Oct 23.


The WalK/WalR (aka YycG/YycF) two-component system (TCS), originally identified in Bacillus subtilis, is very highly conserved and specific to low G+C Gram-positive bacteria, including a number of important pathogens. An unusual feature is that this system is essential for viability in most of these bacteria. Recent studies have revealed conserved functions for this system, defining this signal transduction pathway as a crucial regulatory system for cell wall metabolism, that we have accordingly renamed WalK/WalR. Here we review the cellular role of the WalK/WalR TCS in different bacterial species, focusing on the function of genes in its regulon, as well as variations in walRK operon structure and the composition of its regulon. We also discuss the nature of its essentiality and the potential type of signal being sensed. The WalK histidine kinase of B. subtilis has been shown to localize to the divisome and we suggest that the WalKR system acts as an information conduit between extracytoplasmic cellular structures and intracellular processes required for their synthesis, playing a vital role in effectively co-ordinating peptidoglycan plasticity with the cell division process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacillus subtilis / enzymology
  • Bacillus subtilis / genetics
  • Cell Wall / genetics
  • Cell Wall / metabolism*
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial
  • Gram-Positive Bacteria / enzymology*
  • Gram-Positive Bacteria / genetics*
  • Histidine Kinase
  • Homeostasis
  • Operon / physiology*
  • Peptidoglycan / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Regulon
  • Signal Transduction


  • Peptidoglycan
  • Protein Kinases
  • Histidine Kinase