Recent advances towards identification of new drug targets for Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis is a very successful pathogen that remains a leading infectious killer worldwide. The global situation has become precarious due to various factors such as the variable efficacy of the Bacille Calmette-Guerin (BCG) vaccine, drug resistance, delay in diagnosis, association with HIV, and other factors, creating a long-lasting reservoir of impending disease and infection. Surprisingly, no new drugs have been developed in the past 30 years. The release of the complete genome sequence of M. tuberculosis and the availability of advanced genetic tools have provided the powerful repertoire of potential drug targets that are now in hand and can be explored in a more rational and directional manner. In this review, the authors highlight some possible therapeutic targets in M. tuberculosis. The gene products involved in various processes, such as mycobacterial cell wall synthesis, ability to acquire or obtain essential nutrients, persistence, transcription regulation, energy metabolism and others, such as the PE-PGRS family and culture filtrate proteins, would be potential targets for the development of new drugs. Apart from these categories, the importance of signal transduction events in the virulence of mycobacteria is discussed in relation to their potential as therapeutic targets. The potential of all of these therapeutic targets should be investigated together with the potential of being able to synthesise future chemotherapeutic agents.