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Non-steroidal anti-inflammatory drugs, acetaminophen and ibuprofen, induce phenotypic antibiotic resistance in Escherichia coli: roles of marA and acrB

Verma, Taru and Bhaskarla, Chetana and Sadhir, Ismath and Sreedharan, Syama and Nandi, Dipankar (2018) Non-steroidal anti-inflammatory drugs, acetaminophen and ibuprofen, induce phenotypic antibiotic resistance in Escherichia coli: roles of marA and acrB. In: FEMS MICROBIOLOGY LETTERS, 365 (22).

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Official URL: https://doi.org/10.1093/femsle/fny251

Abstract

The factors contributing to antibiotic resistance in bacteria are an important area of study. Sodium salicylate (NaSal), a non-steroidal anti-inflammatory drug (NSAID), increases antibiotic resistance by inducing the expression of MarA, a transcription factor, which increases the AcrAB-TolC efflux pump. MarA is a substrate of Lon protease and the Delta lon strain displays a high degree of antibiotic resistance. This study was initiated to identify commonly used NSAIDs that may induce antibiotic resistance and to compare their efficacies with NaSal and acetyl salicylic acid (ASA). Quantitative real-time expression analysis revealed induction of marA and acrB by NaSal, ASA, acetaminophen (APAP) and ibuprofen. Further, dose studies demonstrated that NaSal and ASA induce resistance at similar to 2 mM while APAP and ibuprofen induce resistance at similar to 5-10 mM. To dissect the roles of key molecules, atomic force microscopy and functional studies were performed using WT, Delta lon, Delta marA, Delta acrB, Delta lon Delta marA and Delta lon Delta acrB strains. The induction of antibiotic resistance by NaSal, ASA and APAP is relatively higher and is partly dependent on marA, whereas ibuprofen which induces lower antibiotic resistance shows complete marA dependence. Notably, NaSal, ASA, APAP and ibuprofen induce antibiotic resistance in an acrB-dependent manner. The possible significance of some NSAIDs in inducing antibiotic resistance is discussed.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to OXFORD UNIV PRESS
Keywords: antibiotic resistance; atomic force microscopy; bacterial survival; Lon; MarA; NSAIDs
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Biological Sciences > Centre for Infectious Disease Research
Division of Interdisciplinary Research > Centre for Biosystems Science and Engineering
Depositing User: Francis Jayakanth
Date Deposited: 24 Jan 2019 08:51
Last Modified: 24 Jan 2019 08:51
URI: http://eprints.iisc.ac.in/id/eprint/61394

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