Tuberculosis Drug Discovery: Target Identification and Validation

Abstract

Tuberculosis (TB) is a global problem that disproportionately affects a handful of high-burden countries, many of which are located in sub-Saharan Africa. Efforts to combat TB in endemic regions focus on health policy, especially prevention and intervention strategies. Research activities, including those relating to TB drug discovery, are sporadic and, in many cases, driven by the force of a single personality or research group in the absence of a national research agenda. Instead, these countries are often limited to a valuable, but passive, role as research and clinical trial sites for international organizations and pharmaceutical companies. In this chapter, we review current approaches to the identification and validation of potential targets for novel therapeutic interventions against Mycobacterium tuberculosis, an organism that continues to devastate public health systems throughout Africa as causative agent of TB. In addition, we highlight local (South African) research programmes which have contributed to these efforts. Consistent with the significant scientific, technical and financial obstacles confronting TB research, our analysis documents the existence of very few programmes in this region that are dedicated to this challenging, yet fundamental, aspect of TB drug discovery. However, the recent shift internationally to a hybrid model in which academic laboratories drive many aspects of the drug development process—including target identification and validation efforts—in collaboration with major industrial partners holds considerable promise for the expansion of local basic science research programmes in the domain of future TB drug discovery, especially where actively supported by local government.