The challenge of new drug discovery for tuberculosis

Although vaccination has been successful in some countries, tuberculosis (TB) is more prevalent in the world today than ever before, with nearly 10 million new cases expected yearly. Anil Koul and colleagues report on the various new TB drugs and treatment regimens under development. The prospects for some of them are good, they conclude, but the TB pathogen Mycobacterium tuberculosis deploys a range of mechanisms to evade host-control measures, so it will be important to keep the drugs pipeline well supplied. In addition, successful control of TB will depend on economic and societal measures to bolster health-care infrastructure in developing countries where TB is particularly prevalent. Tuberculosis (TB) is more prevalent in the world today than at any other time in human history. Mycobacterium tuberculosis, the pathogen responsible for TB, uses diverse strategies to survive in a variety of host lesions and to evade immune surveillance. A key question is how robust are our approaches to discovering new TB drugs, and what measures could be taken to reduce the long and protracted clinical development of new drugs. The emergence of multi-drug-resistant strains of M. tuberculosis makes the discovery of new molecular scaffolds a priority, and the current situation even necessitates the re-engineering and repositioning of some old drug families to achieve effective control. Whatever the strategy used, success will depend largely on our proper understanding of the complex interactions between the pathogen and its human host. In this review, we discuss innovations in TB drug discovery and evolving strategies to bring newer agents more quickly to patients.