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Abstract
The rise of antimicrobial drug resistance (AMR) in tuberculosis (TB) and non-tubercular mycobacte-
rial (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 carpro-
fen 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 labo-
ratory practice due to the pleiotropic nature of carprofen’s anti-tubercular action. This immunomod-
ulatory drug has the potential to reverse TB antimicrobial drug resistance, offering a prospective path
to clinical trials of novel chemotherapeutic combinations.
References
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