TY - JOUR TI - A cytoplasmic peptidoglycan amidase homologue controls mycobacterial cell wall synthesis AU - Boutte, Cara C AU - Baer, Christina E AU - Papavinasasundaram, Kadamba AU - Liu, Weiru AU - Chase, Michael R AU - Meniche, Xavier AU - Fortune, Sarah M AU - Sassetti, Christopher M AU - Ioerger, Thomas R AU - Rubin, Eric J A2 - Laub, Michael VL - 5 PY - 2016 DA - 2016/06/15 SP - e14590 C1 - eLife 2016;5:e14590 DO - 10.7554/eLife.14590 UR - https://doi.org/10.7554/eLife.14590 AB - 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. KW - peptidoglycan KW - regulation KW - antibiotics KW - Mycobacterium smegmatis KW - Mycobacterium tuberculosis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -