Sheetal Gandotra

CSIR-Institute of Genomics and Integrative Biology, New Delhi, India

Lipid droplets: a comfort zone for Mycobacterium tuberculosis

The human TB granuloma is a lipid rich site where macrophages acquire a distinct “foamy” appearance due to the accumulation of neutral lipids. Our lab has been working on understanding how this environment is created, how it is manipulated by Mycobacterium tuberculosis, and understanding molecular players that help in altering this fate. Using cellular and animal models of infection, we have identified a role of the host enzyme involved in triglyceride synthesis, diacylglycerol O-acyl transferase 1, in neutral lipid accumulation in the TB granuloma. I will be talking about outcomes of inhibiting this function. I will also be discussing mechanisms of active manipulation of the lipid droplet by this intracellular pathogen.

Selected publications

• Ragavendran PV, Tripathi V, Gandotra S. Structure prediction-based insights into the patatin family of Mycobacterium tuberculosis. Microbiology (Reading). 2022 168(12). doi: 10.1099/mic.0.001270
• Dawa S, Menon D, Arumugam P, Bhaskar AK, Mondal M, Rao V, Gandotra S. Inhibition of Granuloma Triglyceride Synthesis Imparts Control of Mycobacterium tuberculosis Through Curtailed Inflammatory Responses. Front Immunol 2021 12:722735
• Menon D, Singh K, Pinto SM, Nandy A, Jaisinghani N, Kutum R, Dash D, Prasad TSK, Gandotra S. Quantitative Lipid Droplet Proteomics Reveals Mycobacterium tuberculosis Induced Alterations in Macrophage Response to Infection. ACS Infect Dis 2019 5(4):559-569
• Jaisinghani N, Dawa S, Singh K, Nandy A, Menon D, Bhandari PD, Khare G, Tyagi A, Gandotra S. Necrosis Driven Triglyceride Synthesis Primes Macrophages for Inflammation During Mycobacterium tuberculosis Infection. Front Immunol 2018 9:1490
• Bothra A, Arumugam P, Panchal V, Menon D, Srivastava S, Shankaran D, Nandy A, Jaisinghani N, Singh A, Gokhale RS, Gandotra S, Rao V. Phospholipid homeostasis, membrane tenacity and survival of Mycobacterium tuberculosis in lipid rich conditions is determined by MmpL11 function. Sci Rep 2018 8(1):8317
• Nandy A, Mondal AK, Pandey R, Arumugam P, Dawa S, Jaisinghani N, Rao V, Dash D, Gandotra S. Adipocyte Model of Mycobacterium tuberculosis Infection Reveals Differential Availability of Iron to Bacilli in the Lipid-Rich Caseous Environment. Infect Immun 2018 86(6):e00041-18