Improved understanding of pathogenesis from protein interactions in Mycobacteriumtuberculosis

Abstract

Comprehensive mapping and analysis of protein–protein interactions provide not only systematic approaches for dissecting the infection and survival mechanisms of pathogens but also clues for discovering new antibacterial drug targets. Protein interaction data on Mycobacterium tuberculosis have rapidly accumulated over the past several years. This review summarizes the current progress of protein interaction studies on M. tuberculosis, the causative agent of tuberculosis. These efforts improve our knowledge on the stress response, signaling regulation, protein secretion and drug resistance of the bacteria. M. tuberculosis–host protein interaction studies, although still limited, have recently opened a new door for investigating the pathogenesis of the bacteria. Finally, this review discusses the importance of protein interaction data on identifying and screening new anti-tuberculosis targets and drugs, respectively.

Keywords::

• drug targets
• Mycobacterium tuberculosis
• pathogen–host interaction
• protein–protein interaction
• stress response

Acknowledgements

T Cui is funded by the National Natural Science Foundation of China (31300079) and the China Postdoctoral Science Foundation (2013M540586). Z-G He is funded by the National Natural Science Foundation of China (31025002 and 81471996), the Hubei Chutian Scholar Program and the Chang Jiang Scholars Program.

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

• Abundant protein interaction data of M. tuberculosis have been accumulated over the past decade.

• Analysis of intraspecies protein interactions has improved our understanding of stress response, cell division and protein secretion of M. tuberculosis.

• Interspecies M. tuberculosis–host protein interactions have uncovered the molecular mechanisms by which this pathogen inhibits immune response and interferes with host phagosome maturation and ROS signaling.

• Multiple methods can be used to identify new antibacterial drug targets from protein interaction data. Disruption of essential protein–protein interactions has been applied in the design of anti-tuberculosis inhibitors.

Notes