Conference Abstract
#1 NSAIDs’ antimicrobial mechanisms of action by inhibiting drug efflux and biofilm formation
274 Views
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
- Maitra A, Evangelopoulos D, Chrzastek A, Martin LT, Hanrath A, Chapman E, Hailes HC, Lip-
- man M, McHugh TD, Waddell SJ, Bhakta S.* (2020) Carprofen elicits pleiotropic mechanisms of
- bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis. J
- Antimicrob Chemother 75(11):3194-3201. DOI: https://doi.org/10.1093/jac/dkaa307
- Lee C, Bhakta S. (2021) The Prospect of Repurposing Immunomodulatory Drugs for Adjunc-
- tive Chemotherapy against Tuberculosis: A Critical Review. Antibiotics (Basel) 10(1):91. DOI:
- https://doi.org/10.3390/antibiotics10010091
- Maitra A, Bates S, Shaik M, Evangelopoulos D, Abubakar I, McHugh TD, Lipman M, Bhakta
- S. (2016) Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-
- inflammatory drugs. Br Med Bull 118(1):138-48. DOI: https://doi.org/10.1093/bmb/ldw019.
- Danquah, C.A.; Maitra, A., Gibbons, S., Faull, J and Bhakta, S. (2016) HT‐SPOTi: a rapid
- drug susceptibility test (DST) to evaluate antibiotic resistance profiles and novel chemi-
- cals for anti‐infective drug discovery. Curr Protoc Microbiol 40 (1), 17.8.1-17.8.12. DOI:
- https://doi.org/10.1002/9780471729259.mc1708s40
Author information
Rights and permissions

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Copyright (c) 2022 Journal of Pharmaceutical Chemistry
About this article
Cite this article
- Received
- January 18, 2022
- Published
- July 20, 2022
- Section
- Conference Abstract