Choudhary Eira, Sharma Rishabh, Pal Pramila, Agarwal Nisheeth
Laboratory of Mycobacterial Genetics, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad121001, Haryana, India.
Symbiosis School of Biomedical Sciences, Symbiosis International (Deemed University), Pune412115, Maharashtra, India.
ACS Omega. 2022 Jul 18;7(30):26749-26766. doi: 10.1021/acsomega.2c03092. eCollection 2022 Aug 2.
The fundamental to the pathogenicity of (Mtb) is the modulation in the control mechanisms that play a role in sensing and counteracting the microbicidal milieu encompassing various cellular stresses inside the human host. To understand such changes, we measured the cellular proteome of Mtb subjected to different stresses using a quantitative proteomics approach. We identified defined sets of Mtb proteins that are modulated in response to acid and a sublethal dose of diamide and HO treatments. Notably, proteins involved in metabolic, catalytic, and binding functions are primarily affected under these stresses. Moreover, our analysis led to the observations that during acidic stress Mtb enters into energy-saving mode simultaneously modulating the acid tolerance system, whereas under diamide and HO stresses, there were prominent changes in the biosynthesis and homeostasis pathways, primarily modifying the resistance mechanism in diamide-treated bacteria while causing metabolic arrest in HO-treated bacilli. Overall, we delineated the adaptive mechanisms that Mtb may utilize under physiological stresses and possible overlap between the responses to these stress conditions. In addition to offering important protein signatures that can be exploited for future mechanistic studies, our study highlights the importance of proteomics in understanding complex adjustments made by the human pathogen during infection.
结核分枝杆菌（Mtb）致病性的根本在于其对调控机制的调节，这些调控机制在感知和对抗包含人类宿主体内各种细胞应激的杀菌环境中发挥作用。为了解此类变化，我们采用定量蛋白质组学方法测量了经受不同应激的Mtb的细胞蛋白质组。我们鉴定出了在响应酸以及亚致死剂量的二酰胺和过氧化氢（HO）处理时发生调节的特定Mtb蛋白组。值得注意的是，参与代谢、催化和结合功能的蛋白质在这些应激条件下受到的影响最为显著。此外，我们的分析得出以下观察结果：在酸性应激期间，Mtb进入节能模式，同时调节耐酸系统；而在二酰胺和HO应激下，生物合成和稳态途径发生显著变化，主要是改变了经二酰胺处理的细菌中的抗性机制，同时导致经HO处理的杆菌出现代谢停滞。总体而言，我们描绘了Mtb在生理应激下可能利用的适应性机制以及这些应激条件响应之间可能存在的重叠。除了提供可用于未来机制研究的重要蛋白质特征外，我们的研究还突出了蛋白质组学在理解人类病原体在感染期间所进行的复杂调节方面的重要性。
