A cytoplasmic peptidoglycan amidase homologue controls mycobacterial cell wall synthesis
Authors
Boutte, Cara C.Baer, Christina E
Papavinasasundaram, Kadamba
Liu, Weiru
Chase, Michael R.
Meniche, Xavier
Fortune, Sarah M.
Sassetti, Christopher M
Ioerger, Thomas R.
Rubin, Eric J.
UMass Chan Affiliations
Department of Microbiology and Physiological SystemsDocument Type
Journal ArticlePublication Date
2016-06-15Keywords
Mycobacterium smegmatisMycobacterium tuberculosis
antibiotics
biochemistry
infectious disease
microbiology
peptidoglycan
regulation
Biochemistry
Microbiology
Metadata
Show full item recordAbstract
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.Source
Elife. 2016 Jun 15;5. pii: e14590. doi: 10.7554/eLife.14590. Link to article on publisher's site
DOI
10.7554/eLife.14590Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39997PubMed ID
27304077Related Resources
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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.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.7554/eLife.14590
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Except where otherwise noted, this item's license is described as 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.