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Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
The effect of commonly used non-antibiotic medications on antimicrobial resistance development in Escherichia coli
Hanbiao Chen1, Sylvia A Sapula1, John Turnidge2
1UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA, Australia.
Abstract:
Antimicrobial resistance (AMR) poses a global threat to public health. While antibiotic overuse is a primary driver, emerging evidence suggests that non-antibiotic medications (NAMs) may also contribute. This concern is particularly relevant in residential aged care facilities (RACFs), where both NAMs and antibiotics are frequently used. We investigated whether nine commonly used NAMs in RACFs, including ibuprofen, diclofenac, acetaminophen, furosemide, metformin, atorvastatin, tramadol, temazepam, and pseudoephedrine at gut-relevant concentrations, enhance ciprofloxacin-induced mutagenesis in Escherichia coli. Our findings showed that ibuprofen and acetaminophen significantly increased mutation frequency and conferred high-level ciprofloxacin resistance. Whole-genome sequencing identified mutations in GyrA, MarR, and AcrR, with the latter two correlated with overexpression of AcrAB-TolC drug efflux pump. Co-exposure to two NAMs further elevated mutation rates and ciprofloxacin resistance levels. This study underscored the overlooked role of NAMs in driving AMR and highlighted the need to reassess polypharmacy risks in aged care settings.
Insights
Common medications like ibuprofen and acetaminophen can increase antibiotic resistance in gut bacteria. This study highlights the risk of non-antibiotic drug use in aged care facilities contributing to antimicrobial resistance (AMR).
Area of Science:
- Microbiology
- Pharmacology
- Public Health
Background:
- Antimicrobial resistance (AMR) is a significant global health threat, primarily driven by antibiotic overuse.
- Non-antibiotic medications (NAMs) are increasingly recognized as potential contributors to AMR.
- Residential aged care facilities (RACFs) frequently use both antibiotics and NAMs, necessitating investigation into their combined effects.
Purpose of the Study:
- To investigate the potential of commonly used NAMs in RACFs to enhance antibiotic-induced mutagenesis.
- To identify specific NAMs that contribute to the development of high-level antibiotic resistance.
Main Methods:
- Exposure of Escherichia coli to gut-relevant concentrations of nine common NAMs (ibuprofen, diclofenac, acetaminophen, furosemide, metformin, atorvastatin, tramadol, temazepam, pseudoephedrine).
- Assessment of mutagenesis and ciprofloxacin resistance.
- Whole-genome sequencing to identify genetic mutations.
- Analysis of drug efflux pump gene expression.
Main Results:
- Ibuprofen and acetaminophen significantly increased mutation frequency and conferred high-level ciprofloxacin resistance in E. coli.
- Whole-genome sequencing revealed mutations in GyrA, MarR, and AcrR genes.
- Mutations in MarR and AcrR correlated with the overexpression of the AcrAB-TolC drug efflux pump.
- Co-exposure to two NAMs further amplified mutation rates and resistance levels.
Conclusions:
- Certain non-antibiotic medications, notably ibuprofen and acetaminophen, can promote antibiotic resistance.
- The study identifies specific genetic mechanisms, including efflux pump upregulation, involved in NAM-mediated AMR.
- Findings underscore the need to evaluate polypharmacy in aged care settings for potential AMR risks.
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