An Integration of Interdisciplinary Translational Research in Anti-TB Drug Discovery: Out of the University Research Laboratories to Combat Mycobacterium tuberculosis

Sanjib Bhakta

doi:10.4172/2168-9547.1000e108

Abstract

Copyright: © 2013 Bhakta S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Tuberculosis (TB) is a dreadful infectious disease responsible for approximately two million human deaths and nine million new cases each year causing massive health and economic impact on global development [1]. One third of the world’s population is latently infected by the pathogen, Mycobacterium tuberculosis. Emergence of total-drug-resistant (TDR)-TB on top of extensively-drug-resistant (XDR) and multidrug-resistant (MDR)-TB is undermining the efforts of many major national and international research consortia such as TB-Drug Discovery, UK (www.tbd-uk.org.uk), Antibiotic Action (www.antibiotic-action.com), New Medicines for Tuberculosis (www. nm4tb.org), Open Source Drug Discovery, India (OSDD; www.osdd. net), EuroLAC-TB consortium (www.eurolactb.org) and the Global TB alliance (www.tballiance.org) to resolve this global human health challenge.

Highlights

Validation of a novel therapeutic target, target based discovery of novel leads and whole cell evaluation of novel chemical entities, are three key interdisciplinary research approaches in preclinical drug discovery
A serine/threonine protein kinase, PrkC in Bacillus subtilis [13], has been reported to act as an effective signal leading to spore germination, which is considered to be a similar physiological process to mycobacterial resuscitation [14]
serine/threonine protein kinases (STPKs) are involved in different metabolic pathways for regulation of cell division, survival inside macrophages, stress responses and hostpathogen interactions in mycobacteria but there is no direct evidence for their involvement in dormancy

Summary

Introduction

Validation of a novel therapeutic target, target based discovery of novel leads and whole cell evaluation of novel chemical entities, are three key interdisciplinary research approaches in preclinical drug discovery. Bioinformatic and structural studies have shown these proteins to be peptidoglycan degrading (hydrolase) enzymes [7,8] and their activity has been verified in vitro [9] and in vivo within M. tuberculosis infected human tissues [10]. The serine/threonine protein kinases (STPKs) are responsible for the regulation of different cellular processes including cell development, survival inside macrophages, stress responses and host-pathogen interactions [12].

Results

Conclusion