Rao Prahlad K, Li Qingbo
Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
Molecules. 2009 Aug 28;14(9):3237-58. doi: 10.3390/molecules14093237.
Understanding the biology of Mycobacterium tuberculosis is one of the primary challenges in current tuberculosis research. Investigation of mycobacterial biology using the systems biology approach has deciphered much information with regard to the bacilli and tuberculosis pathogenesis. The modulation of its environment and the ability to enter a dormant phase are the hallmarks of M. tuberculosis. Until now, proteome studies have been able to understand much about the role of various proteins, mostly in growing M. tuberculosis cells. It has been difficult to study dormant M. tuberculosis by conventional proteomic techniques with very few proteins being found to be differentially expressed. Discrepancy between proteome and transcriptome studies lead to the conclusion that a certain aspect of the mycobacterial proteome is not being explored. Analysis of protein turnover may be the answer to this dilemma. This review, while giving a gist of the proteome response of mycobacteria to various stresses, analyzes the data obtained from abundance studies versus data from protein turnover studies in M. tuberculosis. This review brings forth the point that protein turnover analysis is capable of discerning more subtle changes in protein synthesis, degradation, and secretion activities. Thus, turnover studies could be incorporated to provide a more in-depth view into the proteome, especially in dormant or persistent cells. Turnover analysis might prove helpful in drug discovery and a better understanding of the dynamic nature of the proteome of mycobacteria.
了解结核分枝杆菌的生物学特性是当前结核病研究的主要挑战之一。使用系统生物学方法对分枝杆菌生物学进行的研究已经揭示了许多关于杆菌和结核病发病机制的信息。其对环境的调节以及进入休眠期的能力是结核分枝杆菌的标志。到目前为止，蛋白质组研究已经能够了解各种蛋白质的作用，主要是在生长中的结核分枝杆菌细胞中。通过传统蛋白质组学技术研究休眠的结核分枝杆菌一直很困难，发现差异表达的蛋白质很少。蛋白质组学和转录组学研究之间的差异导致这样的结论：分枝杆菌蛋白质组的某个方面尚未得到探索。蛋白质周转分析可能是解决这一困境的答案。本综述在概述分枝杆菌对各种应激的蛋白质组反应的同时，分析了从丰度研究获得的数据与结核分枝杆菌蛋白质周转研究的数据。本综述提出，蛋白质周转分析能够识别蛋白质合成、降解和分泌活动中更细微的变化。因此，可以纳入周转研究，以更深入地了解蛋白质组，特别是在休眠或持续存在的细胞中。周转分析可能有助于药物发现，并更好地理解分枝杆菌蛋白质组的动态性质。
