Abstract: An effective host immune response is important to control Mycobacterium tuberculosis (Mtb) insult, and to contain its latent persistence. A new paradigm in TB treatment, host-direct therapy (HDT), uses adjunctive drugs to harness intrinsic antimicrobial and immunoregulatory mechanisms for better treatment outcomes. Using chemical genetics approach we have demonstrated that activating AMP-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1), regulators of whole-body energy metabolism, by FDA approved drugs / supplements could control inflammation and Mtb infection. This indicates a deep engagement of Mtb pathogenicity with host’s immuno-metabolic machinery. We hypothesize that the functional connections between immunity and pathways controlling metabolic signaling could be harnessed to advance the HDT pipeline, leading to the development of clinically relevant anti-tuberculosis arsenal. We are utilizing preclinical and clinical models to further understand the molecular and cellular mechanisms of AMPK and SIRT1 activators. The data related to this effort will be presented and discussed

Biography: Dr. Amit Singhal began his career in the field of infectious disease immunology as a PhD fellow at All India institute of Medical Sciences, New Delhi, India. After doing postdoctoral stints at Institute Pasteur, Brussels and Novartis Institute for Tropical Disease, Singapore he joined Singapore Immunology Network in 2011 and started his independent group in 2014. He is applying various basic and advanced omics approaches to understand the mechanisms utilized by bacteria for evading host’s immuno-metabolic signalling. The information gained from these experiments is being currently exploited for designing clinically relevant host-directed therapies.