Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, United States of America.
PLoS Pathog. 2021 Jan 7;17(1):e1009124. doi: 10.1371/journal.ppat.1009124. eCollection 2021 Jan.
Mycobacterial pathogens pose a sustained threat to human health. There is a critical need for new diagnostics, therapeutics, and vaccines targeting both tuberculous and nontuberculous mycobacterial species. Understanding the basic mechanisms used by diverse mycobacterial species to cause disease will facilitate efforts to design new approaches toward detection, treatment, and prevention of mycobacterial disease. Molecular, genetic, and biochemical approaches have been widely employed to define fundamental aspects of mycobacterial physiology and virulence. The recent expansion of genetic tools in mycobacteria has further increased the accessibility of forward genetic approaches. Proteomics has also emerged as a powerful approach to further our understanding of diverse mycobacterial species. Detection of large numbers of proteins and their modifications from complex mixtures of mycobacterial proteins is now routine, with efforts of quantification of these datasets becoming more robust. In this review, we discuss the "genetic proteome," how the power of genetics, molecular biology, and biochemistry informs and amplifies the quality of subsequent analytical approaches and maximizes the potential of hypothesis-driven mycobacterial research. Published proteomics datasets can be used for hypothesis generation and effective post hoc supplementation to experimental data. Overall, we highlight how the integration of proteomics, genetic, molecular, and biochemical approaches can be employed successfully to define fundamental aspects of mycobacterial pathobiology.
分枝杆菌病原体对人类健康构成持续威胁。目前迫切需要针对结核分枝杆菌和非结核分枝杆菌的新型诊断、治疗和疫苗。了解不同分枝杆菌物种引起疾病的基本机制将有助于设计新的方法来检测、治疗和预防分枝杆菌病。分子、遗传和生化方法已广泛用于定义分枝杆菌生理学和毒力的基本方面。分枝杆菌中遗传工具的最近扩展进一步增加了正向遗传方法的可及性。蛋白质组学也已成为深入了解不同分枝杆菌物种的有力方法。现在，从分枝杆菌蛋白质的复杂混合物中检测大量蛋白质及其修饰已成为常规操作，并且对这些数据集进行定量的工作变得更加稳健。在这篇综述中，我们讨论了“遗传蛋白质组”，即遗传学、分子生物学和生物化学的力量如何为后续分析方法提供信息和放大质量，并最大限度地发挥假设驱动的分枝杆菌研究的潜力。已发表的蛋白质组数据集可用于生成假设，并有效地补充实验数据。总的来说，我们强调了如何成功地整合蛋白质组学、遗传、分子和生化方法来定义分枝杆菌病理生物学的基本方面。
