Implications of Mycobacterium tuberculosis Metabolic Adaptability on Drug Discovery and Development

Tuberculosis remains a global health threat that is being exacerbated by the increase in infections attributed to drug resistant Mycobacterium tuberculosis. To combat this, there has been a surge in drug discovery programs to develop new, potent compounds and identify promising drug targets in the pathogen. Two areas of M. tuberculosis biology that have emerged as rich sources of potential novel drug targets are cell wall biosynthesis and energy metabolism. Both processes are important for survival of M. tuberculosis under replicating and nonreplicating conditions. However, both processes are also inherently adaptable under different conditions. Furthermore, cell wall biosynthesis is energy intensive and, thus, reliant on an efficiently functioning energy production system. This Perspective focuses on the interplay between cell wall biosynthesis and energy metabolism in M. tuberculosis, how adaptations in one pathway may affect the other, and what consequences this could have for drug discovery and development and the identification of novel drug targets.