International Conference on Emerging Trends in Drug Discovery and Development (ICETD3-2022)

NSAIDs’ antimicrobial mechanisms of action by inhibiting drug efflux and biofilm formation

20 Jan 2022, 16:15

1h

Birla Institute of Technology

Keynote Lecture Interdisciplinary Keynote Lecture

Speaker

Prof. Sanjib Bhakta (University College of London, Birkbeck)

Description

The rise of antimicrobial drug resistance (AMR) in tuberculosis (TB) and non-tubercular mycobacterial (NTM) infection coupled with the shortage of new antibiotics has elevated the global infectious disease to a major global health priority. Our studies revealed that carprofen, a non-steroidal anti-inflammatory drug (NSAID), inhibited the growth of replicating, non-replicating and multi-drug-resistant clinical isolates of M. tuberculosis. We have approached to investigate the mechanism through which NSAIDs eliminate the infection. Integrative molecular and microbiological inquiries showed that carprofen, a bactericidal drug, inhibited bacterial drug-efflux mechanisms. Carprofen also restricted mycobacterial biofilm-like growth, highlighting the requirement of efflux-mediated communicative systems for the formation of biofilms. Transcriptome profiling revealed that carprofen likely acts by targeting fundamental molecular machine through the disruption of membrane potential, which may explain why spontaneous drug-resistant mutants could not be isolated in laboratory practice due to the pleiotropic nature of carprofen’s anti-tubercular action. This immunomodulatory drug has the potential to reverse TB antimicrobial drug resistance, offering a prospective path to clinical trials of novel chemotherapeutic combinations.

Bibliography:

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