Phosphorylation on PstP Regulates Cell Wall Metabolism and Antibiotic Tolerance in Mycobacterium smegmatis.
Phosphorylation on PstP Regulates Cell Wall Metabolism and Antibiotic Tolerance in Mycobacterium smegmatis.
复制标题
PstP 的磷酸化调节耻垢分枝杆菌的细胞壁代谢和抗生素耐受性。
DOI：
10.1128/jb.00563-20
复制
发表时间：
2021
影响因子：
3.2
通讯作者：
Boutte,CaraC
中科院分区：
文献类型：
--
作者：
Shamma,Farah;Papavinasasundaram,Kadamba;Quintanilla,SamanthaY;Bandekar,Aditya;Sassetti,Christopher;Boutte,CaraC
结核分枝杆菌和它的亲戚，像许多细菌一样，有动态的细胞壁，对环境压力作出反应。在应激中细胞壁代谢的调节被认为是导致渗透性降低和对抗生素耐受性增加的原因。然而，在压力下控制细胞壁代谢的信号系统却知之甚少。在这里，我们研究了细胞壁的调节功能的一个关键的细胞壁调节剂，丝氨酸/苏氨酸磷酸酶PstP，在模式生物耻垢分枝杆菌。我们表明，肽聚糖调节CwlM是PstP的底物。我们发现一个磷酸模拟突变，pstPT 171 E，减缓生长，在不同条件下错误调节分枝菌酸和肽聚糖代谢，并干扰抗生素耐受性。这些数据表明，PstP上的磷酸化影响其对各种底物的活性，是重要的生长和stasis.IMPORTANCERegulation之间的过渡细胞壁组装是必不可少的细菌的生存，并有助于发病机制和抗生素耐药性的分枝杆菌，包括病原体，如结核分枝杆菌。然而，很少有人知道细胞壁是如何调节压力。我们描述了耻垢分枝杆菌细胞壁调节的途径，通过唯一的必需的丝氨酸/苏氨酸磷酸酶，PstP。我们发现PstP的磷酸化在调节向停滞过渡的肽聚糖代谢和生长中的分枝菌酸代谢中是重要的。这种调节也影响生长和停滞中的抗生素耐受性。这项工作有助于我们更好地了解磷酸化介导的细胞壁调控回路在分枝杆菌。
Mycobacterium tuberculosis and its relatives, like many bacteria, have dynamic cell walls that respond to environmental stresses. Modulation of cell wall metabolism in stress is thought to be responsible for decreased permeability and increased tolerance to antibiotics. The signaling systems that control cell wall metabolism under stress, however, are poorly understood. Here, we examine the cell wall regulatory function of a key cell wall regulator, the serine/threonine phosphatase PstP, in the model organism Mycobacterium smegmatis. We show that the peptidoglycan regulator CwlM is a substrate of PstP. We find that a phosphomimetic mutation,pstPT171E, slows growth, misregulates both mycolic acid and peptidoglycan metabolism in different conditions, and interferes with antibiotic tolerance. These data suggest that phosphorylation on PstP affects its activity against various substrates and is important in the transition between growth and stasis.IMPORTANCERegulation of cell wall assembly is essential for bacterial survival and contributes to pathogenesis and antibiotic tolerance in mycobacteria, including pathogens such as Mycobacterium tuberculosis. However, little is known about how the cell wall is regulated in stress. We describe a pathway of cell wall modulation in Mycobacterium smegmatis through the only essential Ser/Thr phosphatase, PstP. We showed that phosphorylation on PstP is important in regulating peptidoglycan metabolism in the transition to stasis and mycolic acid metabolism in growth. This regulation also affects antibiotic tolerance in growth and stasis. This work helps us to better understand the phosphorylation-mediated cell wall regulation circuitry inMycobacteria.