Department of Microbiology and Physiological Systems; UMass Metabolic Network
Biochemistry | Microbiology
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.
Mycobacterium smegmatis, Mycobacterium tuberculosis, antibiotics, biochemistry, infectious disease, microbiology, peptidoglycan, regulation
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Copyright © 2016, Boutte et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Elife. 2016 Jun 15;5. pii: e14590. doi: 10.7554/eLife.14590. Link to article on publisher's site
Boutte, Cara C.; Baer, Christina E.; Papavinasasundaram, Kadamba; Liu, Weiru; Chase, Michael R.; Meniche, Xavier; Fortune, Sarah M.; Sassetti, Christopher M.; Ioerger, Thomas R.; and Rubin, Eric J., "A cytoplasmic peptidoglycan amidase homologue controls mycobacterial cell wall synthesis" (2016). Open Access Articles. 2806.
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