Two Faces of CwIM, an Essential PknB Substrate, in<i> Mycobacterium tuberculosis</i>

Turapov, Obolbek, Forti, Francesca, Kadhim, Baleegh, Ghisotti, Daniela, Sassine, Jad, Straatman-Iwanowska, Anna, Bottrill, Andrew R, Moynihan, Patrick J, Wallis, Russell, Barthe, Philippe
et al (show 4 more authors) (2018) Two Faces of CwIM, an Essential PknB Substrate, in<i> Mycobacterium tuberculosis</i>. CELL REPORTS, 25 (1). 57-+.

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Tuberculosis claims >1 million lives annually, and its causative agent Mycobacterium tuberculosis is a highly successful pathogen. Protein kinase B (PknB) is reported to be critical for mycobacterial growth. Here, we demonstrate that PknB-depleted M. tuberculosis can replicate normally and can synthesize peptidoglycan in an osmoprotective medium. Comparative phosphoproteomics of PknB-producing and PknB-depleted mycobacteria identify CwlM, an essential regulator of peptidoglycan synthesis, as a major PknB substrate. Our complementation studies of a cwlM mutant of M. tuberculosis support CwlM phosphorylation as a likely molecular basis for PknB being essential for mycobacterial growth. We demonstrate that growing mycobacteria produce two forms of CwlM: a non-phosphorylated membrane-associated form and a PknB-phosphorylated cytoplasmic form. Furthermore, we show that the partner proteins for the phosphorylated and non-phosphorylated forms of CwlM are FhaA, a fork head-associated domain protein, and MurJ, a proposed lipid II flippase, respectively. From our results, we propose a model in which CwlM potentially regulates both the biosynthesis of peptidoglycan precursors and their transport across the cytoplasmic membrane.

Item Type: Article
Uncontrolled Keywords: Cell Wall, Mycobacterium tuberculosis, N-Acetylmuramoyl-L-alanine Amidase, Amino Acid Sequence, Phosphorylation, Proto-Oncogene Proteins c-akt
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 31 Mar 2022 07:39
Last Modified: 16 Mar 2024 02:05
DOI: 10.1016/j.celrep.2018.09.004
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