Mycobacterial serine/threonine phosphatase PstP is phosphoregulated and localized to mediate control of cell wall metabolism,Molecular Microbiology

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Mycobacterial serine/threonine phosphatase PstP is phosphoregulated and localized to mediate control of cell wall metabolism
Molecular Microbiology ( IF 2.6 ) Pub Date : 2022-06-07 , DOI: 10.1111/mmi.14951
Farah Shamma ₁ , E Hesper Rego ₂ , Cara C Boutte ₁

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The mycobacterial cell wall is profoundly regulated in response to environmental stresses, and this regulation contributes to antibiotic tolerance. The reversible phosphorylation of different cell wall regulatory proteins is a major mechanism of cell wall regulation. Eleven serine/threonine protein kinases phosphorylate many critical cell wall-related proteins in mycobacteria. PstP is the sole serine/ threonine phosphatase, but few proteins have been verified as PstP substrates. PstP is itself phosphorylated, but the role of its phosphorylation in regulating its activity has been unclear. In this study, we aim to discover novel substrates of PstP in Mycobacterium tuberculosis (Mtb). We show in vitro that PstP dephosphorylates two regulators of peptidoglycan in Mtb, FhaA, and Wag31. We also show that a phosphomimetic mutation of T137 on PstP negatively regulates its catalytic activity against the cell wall regulators FhaA, Wag31, CwlM, PknB, and PknA, and that the corresponding mutation in Mycobacterium smegmatis causes misregulation of peptidoglycan in vivo. We show that PstP is localized to the septum, which likely restricts its access to certain substrates. These findings on the regulation of PstP provide insight into the control of cell wall metabolism in mycobacteria.

中文翻译：

分枝杆菌丝氨酸/苏氨酸磷酸酶 PstP 被磷酸调节和定位以介导细胞壁代谢的控制

分枝杆菌细胞壁受到环境压力的深刻调节，这种调节有助于抗生素耐受性。不同细胞壁调节蛋白的可逆磷酸化是细胞壁调节的主要机制。十一种丝氨酸/苏氨酸蛋白激酶磷酸化分枝杆菌中许多关键的细胞壁相关蛋白。PstP 是唯一的丝氨酸/苏氨酸磷酸酶，但很少有蛋白质被证实为 PstP 底物。PstP 本身被磷酸化，但其磷酸化在调节其活性中的作用尚不清楚。在这项研究中，我们旨在发现结核分枝杆菌( Mtb ) 中 PstP 的新底物。我们在体外表明 PstP 使Mtb中的两种肽聚糖调节剂去磷酸化、FhaA 和 Wag31。我们还表明，PstP 上 T137 的拟磷酸化突变会负向调节其对细胞壁调节因子 FhaA、Wag31、CwlM、PknB 和 PknA 的催化活性，并且耻垢分枝杆菌中的相应突变会导致体内肽聚糖的错误调节。我们表明 PstP 定位于隔膜，这可能会限制其对某些底物的访问。这些关于 PstP 调节的发现提供了对分枝杆菌细胞壁代谢控制的深入了解。

更新日期：2022-06-07

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