Omics and Computational Chemistry Reveal Environmental Residues of Anti-COVID-19 Drug Chloroquine Phosphate Drive Antibiotic Resistance Gene Dissemination

ABSTRACT: The widespread use of chloroquine phosphate (CQP) during the COVID-19 pandemic has led to its persistent residues in aquatic environments, yet its impact on the horizontal transfer of antibiotic resistance genes (ARGs) remains unknown. Herein, the effects and molecular mechanisms of CQP on plasmid-mediated ARGs transfer using an E. coli conjugation model and natural aquatic microbial communities were investigated. Environmentally relevant CQP concentrations (<1.0 mg/L) significantly promoted the conjugative transfer of ARGs, with a maximum 1.42 fold increase at 1.0 mg/L, while higher concentrations (4.0 mg/L) inhibited ARGs transfer. This biphasic effect was independent of bacterial viability and conserved in complex lake water. Mechanistically, low dose CQP induced moderate oxidative stress, activated the SOS response, increased membrane permeability, upregulated pilus and quorum sensing related genes, and enhanced ATP production. Molecular docking and density functional theory further revealed that CQP bond to key conjugation proteins (AcrB and TraD) and possessed electron accepting capacity, facilitating membrane interactions. Comprehensive transcriptomic and metabolomic analyses showed CQP remodeled membrane lipid and optimized donor-recipient contact. This study uncovers a hidden antimicrobial resistance risk of residual CQP, highlighting the need to concern post-pandemic pharmaceutical pollution risks in wastewater treatment.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS15990 | MetaboLights | 2026-10-10

REPOSITORIES: MetaboLights