Babele Prabhakar, Midha Mukul K, Rao Kanury V S, Kumar Ajay
Translational Health Science and Technology Institute, Faridabad 121001, India.
Institute for Systems Biology, Seattle, WA 98109, USA.
Microorganisms. 2023 Dec 16;11(12):2998. doi: 10.3390/microorganisms11122998.
Apart from being preventable and treatable, tuberculosis is the deadliest bacterial disease afflicting humankind owing to its ability to evade host defence responses, many of which are controlled by epigenetic mechanisms. Here, we report the temporal dynamics of the proteome of macrophage-like host cells after infecting them for 6, 18, 30, and 42 h with two laboratory strains (H37Ra and H37Rv) and two clinical strains (BND433 and JAL2287) of (MTB). Using SWATH-MS, the proteins characterized at the onset of infection broadly represented oxidative stress and cell cytoskeleton processes. Intermediary and later stages of infection are accompanied by a reshaping of the combination of proteins implicated in histone stability, gene expression, and protein trafficking. This study provides strain-specific and time-specific variations in the proteome of the host, which might further the development of host-directed therapeutics and diagnostic tools against the pathogen. Also, our findings accentuate the importance of proteomic tools in delineating the complex recalibration of the host defence enabled as an effect of MTB infection. To the best of our knowledge, this is the first comprehensive proteomic account of the host response to avirulent and virulent strains of MTB at different time periods of the life span of macrophage-like cells. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE repository with the dataset identifier PXD022352.
除了具有可预防性和可治疗性外，结核病是困扰人类的最致命细菌性疾病，因为它能够逃避宿主防御反应，其中许多反应是由表观遗传机制控制的。在这里，我们报告了用结核分枝杆菌（MTB）的两种实验室菌株（H37Ra和H37Rv）以及两种临床菌株（BND433和JAL2287）感染巨噬细胞样宿主细胞6、18、30和42小时后，宿主细胞蛋白质组的时间动态变化。使用SWATH-MS技术，在感染开始时鉴定出的蛋白质广泛代表氧化应激和细胞细胞骨架过程。感染的中期和后期伴随着与组蛋白稳定性、基因表达和蛋白质运输相关的蛋白质组合的重塑。这项研究提供了宿主蛋白质组中菌株特异性和时间特异性的变化，这可能会推动针对该病原体的宿主导向疗法和诊断工具的开发。此外，我们的研究结果强调了蛋白质组学工具在描绘MTB感染导致的宿主防御复杂重新校准中的重要性。据我们所知，这是首次对巨噬细胞样细胞生命周期不同时间段内宿主对MTB无毒和有毒菌株的反应进行全面的蛋白质组学描述。质谱蛋白质组学数据已通过PRIDE储存库存入蛋白质组交换联盟，数据集标识符为PXD022352。
