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

Keywords

aaa

How to Cite

(1)
Bhakta, S. #1 NSAIDs’ Antimicrobial Mechanisms of Action by Inhibiting Drug Efflux and Biofilm Formation. J Pharm Chem 2022, 8.

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

Creative Commons License

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Copyright (c) 2022 Journal of Pharmaceutical Chemistry