Séminaire CIRI (27.05.2024): Pr. Raju MUKHERJEE

Pr. Raju MUKHERJEE, IISER Tirupati (Inde), “ Complex mechanism of antibiotic action in mycobacteria ”      

Abstract: Antibiotic-tolerant bacteria, due to their unique physiology, are refractory to antimicrobial killing and pose challenges for infection control. Incomplete knowledge of how bactericidal antibiotics work, limits our understanding of partial resistance due to phenotypic tolerance in mycobacteria, a driver for developing genetic resistance. Using proteomics, 13C isotopomer analysis, genetic and biochemical assays, we investigated the physiological response of mycobacteria challenged with antibiotics.  Distinct classes of antibiotics elicited remarkably similar responses and increased flux through the TCA cycle, causing enhanced respiration, ROS generation, and ATP burst. We observed that excessive ATP levels and not ROS, dominantly contributes to cidality, which may in part be, conferred by sequestration of divalent metal ions by ATP.  In this talk I will provide a new understanding of the intricate mechanisms of antibiotic-induced cell death and expand the current paradigm for antibiotic action.

Hôte : Nicolas Personnic