U1019 - UMR9017 - CIIL - Center for Infection and Immunity of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Université de Lille, France.
FEBS J. 2020 Oct;287(20):4415-4426. doi: 10.1111/febs.15232. Epub 2020 Feb 12.
Protein-protein interactions are key in mycobacterial physiology, notably during the biosynthesis of the very peculiar mycobacterial cell wall. In this paper, we demonstrate that MSMEG_1285 interacts with PonA1, a bifunctional penicillin-binding protein involved in peptidoglycan biosynthesis. Deletion of MSMEG_1285 enhances Mycobacterium smegmatis resistance to penicillin antibiotics, a phenotype that is exacerbated by the additional deletion of hbhA. This also led to a substantial decrease in the amounts of porins in the cell wall, which are necessary for the import of small and hydrophilic β-lactams. Deletion of both MSMEG_1285 and hbhA provoked an over-representation of several enzymes involved in peptidoglycan degradation. Thus, we propose that MSMEG_1285 is part of a protein scaffold, which also involves PonA1 and HbhA, and that it is responsible for the tight regulation of peptidoglycan hydrolysis. This study provides a better understanding of the mycobacterial physiology, which is an essential step for strengthening the action of drugs that specifically target peptidoglycan biosynthesis.
蛋白质-蛋白质相互作用是分枝杆菌生理学的关键，特别是在非常特殊的分枝杆菌细胞壁的生物合成过程中。在本文中，我们证明了 MSMEG_1285 与 PonA1 相互作用，PonA1 是一种参与肽聚糖生物合成的双功能青霉素结合蛋白。MSMEG_1285 的缺失增强了分枝杆菌对青霉素抗生素的抗性，这种表型在 hbhA 缺失的情况下会加剧。这也导致细胞壁中孔蛋白的数量大量减少，孔蛋白对于小分子和亲水β-内酰胺的导入是必需的。MSMEG_1285 和 hbhA 的双重缺失引发了参与肽聚糖降解的几种酶的过度表达。因此，我们提出 MSMEG_1285 是一个蛋白质支架的一部分，该支架还涉及 PonA1 和 HbhA，它负责严格调节肽聚糖水解。这项研究为理解分枝杆菌生理学提供了更好的认识，这是增强专门针对肽聚糖生物合成的药物作用的重要步骤。
