Environmental Consequences of Anthropogenic Pollution: Non-antibiotic-Drug-Driven Antibiotic Resistance Selection in...

Non-antibiotic drugs (NADs) used in human therapy may induce antibiotic resistance selection and dissemination in vitro. However, the potential risks of antibiotic resistance emergence associated with environmental NAD pollution have not been addressed. Here, we conducted a multidisciplinary study on river water microcosms using growth kinetics, qPCR, metagenomics, 16S rRNA sequencing, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine whether NADs alter river bacterial ecology and select for antibiotic resistance genes (ARGs). Four NADs with different mechanisms of action were included at a high (mg/L) and low (μg/L) dose to establish dose-response relationships: chlorpromazine (antipsychotic), diclofenac (anti-inflammatory), diphenhydramine (antihistamine), and fluoxetine (antidepressant). Although the community response to NAD pollution was compound-specific and dose-dependent, all NADs and doses were stable in the environment, altered the composition and activity of bacterial communities, and selected for several ARGs, mostly β-lactamases and aminoglycoside resistance genes, some of which were associated with horizontal gene transfer genes. Pseudomonas (including some ARG-harboring subpopulations) was identified as a key player in the response to NAD pollution. Here, we demonstrate NAD-driven antibiotic resistance selection in complex aquatic communities, raising concerns about the collateral effects on human and environmental health due to the extensive anthropocentric use of NADs.