Abstract
Bacterial cells are encased in a peptidoglycan (PG) exoskeleton that protects them from osmotic lysis and specifies their distinct shapes. Cell wall hydrolases are required to enlarge this covalently closed macromolecule during growth, but how these autolytic enzymes are regulated remains poorly understood. Bacillus subtilis encodes two functionally redundant D,L-endopeptidases (CwlO and LytE) that cleave peptide crosslinks to allow expansion of the PG meshwork during growth. Here, we provide evidence that the essential and broadly conserved WalR-WalK two component regulatory system continuously monitors changes in the activity of these hydrolases by sensing the cleavage products generated by these enzymes and modulating their levels and activity in response. The WalR-WalK pathway is conserved among many Gram-positive pathogens where it controls transcription of distinct sets of PG hydrolases. Cell wall remodeling in these bacteria may be subject to homeostatic control mechanisms similar to the one reported here.
Highlights
The cell wall peptidoglycan (PG) is composed of long glycan strands cross-linked together by short peptides
LytE levels increase in the absence of CwlO maintaining cell envelope integrity In the course of characterizing LytE protein levels in various mutant backgrounds, we discovered that LytE levels increase approximately 2-fold in the absence of CwlO (Figure 1A)
To determine whether this increase was due to changes in lytE transcription, we fused the lytE promoter to lacZ and compared ß-galactosidase activity in wild-type and cells lacking CwlO
Summary
The cell wall peptidoglycan (PG) is composed of long glycan strands cross-linked together by short peptides. This three-dimensional exoskeleton specifies shape and protects the cell from osmotic rupture. We report that the WalR-WalK (WalRK) two-component signaling pathway functions in the homeostatic control of the cell wall hydrolases required for expansion of the PG during growth. Cells engineered to constitutively express a subset of these enzymes can bypass the essentiality of the signaling pathway (Ng et al, 2003; Delaune et al, 2011; Takada et al, 2018).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
