Mycobacterial proteomics: analysis of expressed proteomes and post-translational modifications to identify candidate virulence factors

Abstract

The Mycobacterium tuberculosis bacillus has a number of unique features that make it a particularly effective human pathogen. Although genomic analysis has added to our current understanding of the molecular basis by which M. tuberculosis damages its host, proteomics may be better suited to describe the dynamic interactions between mycobacterial and host systems that underpin this disease. The M. tuberculosis proteome has been investigated using proteomics for over a decade, with increasingly sophisticated mass spectrometry technology and sensitive methods for comparative proteomic profiling. Deeper coverage of the M. tuberculosis proteome has led to the identification of hundreds of putative virulence determinants, as well as an unsurpassed coverage of post-translational modifications. Proteomics is therefore uniquely poised to contribute to our understanding of this pathogen, which may ultimately lead to better management of the disease.

Keywords:

• bacterial proteomics
• mass spectrometry
• Mycobacterium tuberculosis
• pathogenicity
• proteomics
• virulence

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Proteomic studies of virulence allow for wider scale assessment compared to classical studies.

• Mycobacterial virulence is a complex interaction between the host, pathogen and environment and is better understood by global approaches such as proteomics, provided that there is a matching quantitative clinical description of such virulence.

• Label-based and label-free quantitative proteomic approaches each have their own strengths and limitations.

• Mycobacterial virulence factors are likely to occur at low abundance and proteomic studies of Mycobacterium tuberculosis may require enrichment for subproteomes or targeted approaches.

• Protein modifications in mycobacteria, including glycosylation, phosphorylation and acetylation, are thought to confer virulence in M. tuberculosis and are best studied using mass spectrometry.

• Temporal dynamics of mycobacterial expression and modification are likely to be important in modulating interaction with the host immune system.

• Culture-free methods to analyze M. tuberculosis bacilli isolated from the site of disease may enable more meaningful insight into the expression of mycobacterial virulence factors.

• A large number of M. tuberculosis proteins with unknown function may be important virulent factors and these proteins therefore warrant detailed functional analysis.