Work

Inflammasome activation dictates the efficacy of antimycobacterial activity of frontline TB drugs

Year: 2026

Type: article

Abstract: Recent developments in tuberculosis (TB) treatment have identified an enormous potential of host-directed therapies (HDT)) in achieving better and faster control of infection. We have previously demonstrated the synergistic effect of sertraline (SRT) with frontline TB drugs in clearing infection in murine tissues. Our attempts to uncover the mechanistic basis of this enhancement, using sertraline as a probe, help identify host signalling pathways critical for controlling Mycobacterium tuberculosis (Mtb). We identify a significant role for sertraline-mediated modulation of mitochondrial physiology and consequent reactive oxygen species (ROS) generation as a secondary signal, leading to greater IL-1β release and K+ efflux from macrophages via NLRP3 inflammasome activation. We thus highlight an important relationship between mitochondrial physiology and inflammasome activation, enabling infected macrophages to better control Mtb.

Source: PLoS Pathogens

DOI: 10.1371/journal.ppat.1014384

Authors: Anjali Singh, Kanika Bisht, Garima Maurya, Nidhi Yadav, Ranjan Nanda, Vivek Rao

Institutions: Institute of Genomics and Integrative Biology, Academy of Scientific and Innovative Research, International Centre for Genetic Engineering and Biotechnology

Language: English

Topic: Tuberculosis Research and Epidemiology

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,043