A cytoplasmic peptidoglycan amidase homologue controls mycobacterial cell wall synthesis
- Harvard T.H. Chan School of Public Health, United States
- University of Massachusetts Medical School, United States
- Texas A&M University, United States
- Harvard TH Chan School of Public Health, United States
Abstract
Regulation of cell wall assembly is essential for bacterial survival and contributes to pathogenesis and antibiotic tolerance in Mycobacterium tuberculosis (Mtb). However, little is known about how the cell wall is regulated in stress. We found that CwlM, a protein homologous to peptidoglycan amidases, coordinates peptidoglycan synthesis with nutrient availability. Surprisingly, CwlM is sequestered from peptidoglycan (PG) by localization in the cytoplasm, and its enzymatic function is not essential. Rather, CwlM is phosphorylated and associates with MurA, the first enzyme in PG precursor synthesis. Phosphorylated CwlM activates MurA ~30 fold. CwlM is dephosphorylated in starvation, resulting in lower MurA activity, decreased cell wall metabolism, and increased tolerance to multiple antibiotics. A phylogenetic analysis of cwlM implies that localization in the cytoplasm drove the evolution of this factor. We describe a system that controls cell wall metabolism in response to starvation, and show that this regulation contributes to antibiotic tolerance.
Article and author information
Author details
Reviewing Editor
- Michael Laub, Massachusetts Institute of Technology, United States
Version history
- Received: January 21, 2016
- Accepted: June 14, 2016
- Accepted Manuscript published: June 15, 2016 (version 1)
- Version of Record published: July 15, 2016 (version 2)
Copyright
© 2016, Boutte et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A cytoplasmic peptidoglycan amidase homologue controls mycobacterial cell wall synthesis
eLife 5:e14590.
https://doi.org/10.7554/eLife.14590
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