Abstract

Antibiotic resistance is a serious global threat for public health. Considering the high abundance of cell-free DNA encoding antibiotic resistance genes (ARGs) in both clinical and environmental settings, natural transformation is an important horizontal gene transfer pathway to transmit antibiotic resistance. It is acknowledged that antibiotics are key drivers for disseminating antibiotic resistance, yet the contributions of non-antibiotic pharmaceuticals on transformation of ARGs are overlooked. In this study, we report that some commonly consumed non-antibiotic pharmaceuticals, at clinically and environmentally relevant concentrations, significantly facilitated the spread of antibiotic resistance through the uptake of exogenous ARGs. This included nonsteroidal anti-inflammatories, ibuprofen, naproxen, diclofenac, the lipid-lowering drug, gemfibrozil, and the β-blocker propranolol. Based on the results of flow cytometry, whole-genome RNA sequencing and proteomic analysis, the enhanced transformation of ARGs was affiliated with promoted bacterial competence, enhanced stress levels, over-produced reactive oxygen species and increased cell membrane permeability. In addition, a mathematical model was proposed and calibrated to predict the dynamics of transformation during exposure to non-antibiotic pharmaceuticals. Given the high consumption of non-antibiotic pharmaceuticals, these findings reveal new concerns regarding antibiotic resistance dissemination exacerbated by non-antibiotic pharmaceuticals.

Highlights

  • Antibiotic resistance is not a new phenomenon, but the recent increasing prevalence of antibiotic resistant bacteria and antibiotic resistance genes (ARGs) is unprecedented [1, 2]

  • The transformation systems were established by applying free plasmid pWH1266, encoding resistance against tetracycline and ampicillin, to the bacterial inoculum A. baylyi

  • We found that the exposure of non-antibiotic pharmaceuticals caused large-scale changes in the expression of TonB-related proteins and genes

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Summary

Introduction

Antibiotic resistance is not a new phenomenon, but the recent increasing prevalence of antibiotic resistant bacteria and antibiotic resistance genes (ARGs) is unprecedented [1, 2]. Drug-resistant strains of bacteria first appeared in hospitals where most antibiotics are being used [3]. They are frequently detected in the wider environments of water, soil and air [4,5,6].

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