Protein turnover in mycobacterial proteomics

Abstract

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.

Figure 1

Protein relative abundance and turnover of iron-starved M. tuberculosis cells in response to a high-iron (HI) and low-iron (LI) condition. The abundance of a protein is represented by an extracted ion-chromatographic intensity (A). A protein is quantified for its old fraction abundance (A_L), new fraction abundance (A_M), and total abundance (A_T). A_T is the sum of A_L and A_M. A_M/A_L represents the S/D i.e., protein turnover. The three M-A plot panels illustrate the total abundance ratios of protein between the HI and LI cells (Panel A), the protein turnover in the HI cells (Panel B), and the protein turnover in the LI cells (Panel C) respectively. Those proteins with a >2-fold change (p < 0.05) in total abundance ratio or turnover are marked with black triangles and diamonds. Adapted from reference [56] with permission.