A cytoplasmic peptidoglycan amidase homologue controls mycobacterial cell wall synthesis. Academic Article uri icon

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.

published proceedings

  • Elife

altmetric score

  • 4.85

author list (cited authors)

  • Boutte, C. C., Baer, C. E., Papavinasasundaram, K., Liu, W., Chase, M. R., Meniche, X., ... Rubin, E. J.

citation count

  • 72

complete list of 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

publication date

  • June 2016

published in