Sirtuin Deacetylases: Linking Mycobacterial Infection and Host Metabolism

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), primarily targets macrophages and actively modulates the host response through intricate mechanisms ranging from immune evasion to perturbation of cellular metabolism. These cellular immuno-metabolic processes are intrinsically linked via key energy sensors, including sirtuins, a family of conserved NAD+-dependent deacetylases. Recent evidence suggests that Mtb has evolved to manipulate host cell metabolism by modulating the activity of sirtuins. Here, we briefly discuss the mammalian sirtuins with focus on the role of sirtuins during inflammation and fibrosis, which are cornerstones of TB pathogenesis. Finally, we highlight the importance of sirtuins as targets of TB host-directed therapies.