In order to survive,
bacteria have developed avariety of highly sophisticated and sensitive
signal transduction pathways with which they adapt their
genetic expression to meet the challenges of their ever-changing surroundings. These mechanisms enable
bacterial cells to communicate with their environment, their hosts and each other, allowing them adopt specific responses, or develop specialised structures such as
biofilms or
spores to ensure survival, colonization of their ecological niches and dissemination. As highlighted in this book, the so-called
two-component systems (TCSs) are one of the most widespread and efficient strategies used for this purpose, where signal acquisition involves autophosphorylation of a sensor
histidine kinase and transduction takes place when the
kinase phosphorylates its cognate response
regulator protein, leading in turn to specific alteration ofgene expression. In their simplest form, TCSs elegantly combine sensing, transducing and transcription
activation modules within two proteins, effectively coupling external signals to
genetic adaptation. The high degree of conservation among TCS phosphotransfer domains, their ubiquitous nature and the fact that several are essential for cell viability has made them an attractive target for novel classes of
antimicrobial compounds. The WalK/WalR (aka YycG/YycF)
two-component system, originally identified in
Bacillus subtilis, is very
highly conserved and specific to low G + C
Gram-positive bacteria, including several
pathogens such as
Staphylococcus aureus. While this system is essential for cell viability, both the nature of its
regulon and its physiological role had remained mostly uncharacterized. A number of recent studies have now unveiled a conserved function for this system in different
bacteria, defining this
signal transduction pathway as a master regulatory system for
cell wall metabolism, which we have accordingly renamed WalK/WalR. This review will focus on the cellular function of the WalK/WalR TCS in different
bacterial species and the attractive target it constitutes for novel classes of
antimicrobial compounds.
