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Many antibiotics target the assembly of cell wall peptidoglycan, an essential, heteropolymeric mesh that encases most bacteria. In rod-shaped bacteria, cell wall elongation is spatially precise yet relies on limited pools of lipid-linked precursors that generate and are attracted to membrane disorder. By tracking enzymes, substrates, and products of peptidoglycan biosynthesis in Mycobacterium smegmatis, we show that precursors are made in plasma membrane domains that are laterally and biochemically distinct from sites of cell wall assembly. Membrane partitioning likely contributes to robust, orderly peptidoglycan synthesis, suggesting that these domains help template peptidoglycan synthesis. The cell wall-organizing protein DivIVA and the cell wall itself promote domain homeostasis. These data support a model in which the peptidoglycan polymer feeds back on its membrane template to maintain an environment conducive to directional synthesis. Our findings are applicable to rod-shaped bacteria that are phylogenetically distant from M. smegmatis, indicating that horizontal compartmentalization of precursors may be a general feature of bacillary cell wall biogenesis.
Morita, Yasu/0000-0002-4514-9242; Judd, Julius/0000-0002-4602-0205; Siegrist, Sloan/0000-0002-8232-3246; Kado, Takehiro/0000-0001-5419-6123; /0000-0002-9573-4087
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National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AI144748, U01 CA221230, DP2 AI138238, R03 AI140259-01, R01 AI097191]; Universidad Autonoma de Nuevo Leon; Uehara Memorial FoundationUehara Memorial Foundation; Coordenacao de Aperfeicoamento de Pessoal de Nivel SuperiorCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [0328-13-8]
García-Heredia, Alam; Kado, Takehiro; Sein, Caralyn E.; Puffal, Julia; Osman, Sarah H.; Judd, Julius; Gray, Todd A.; Morita, Yasu S.; and Siegrist, M. Sloan, "Membrane-Partitioned Cell Wall Synthesis in Mycobacteria" (2021). ELIFE SCIENCES PUBLICATIONS LTD. 340.