Exposure to the Broad-Spectrum Disinfectant Glutaraldehyde Facilitates Antibiotic Resistance Genes Dissemination via Plasmid-Mediated Conjugation.

Plasmid-mediated conjugative transfer is a major driver of antibiotic resistance genes (ARGs) dissemination, posing serious risks to ecosystems and human health. Glutaraldehyde (GA), a widely used disinfectant, is increasingly detected in environmental matrices, raising emerging concerns regarding its potential to promote ARGs spread. However, whether GA influences plasmid transfer remains largely unknown. Here, we showed that environmentally relevant concentrations of GA (0.01-1 mg/L) significantly enhanced the conjugative transfer of the multidrug resistance plasmid pKJK5 across both intra- and inter-genus bacterial systems. GA increased transfer frequencies by up to 4.29-fold in pure cultures and 4.16-fold in wastewater microbial communities, facilitating ARGs dissemination to diverse taxa, including several opportunistic pathogens. Mechanistically, GA damaged the integrity of the cell membrane , induced ROS production and the SOS response, promoted cell motility and biofilm formation, and upregulated genes involved in ROS detoxification, SOS regulation, membrane permeability, and conjugation. Nontargeted metabolomics profiling and molecular docking further supported these observations. Our findings reveal a previously overlooked role of GA in accelerating ARGs dissemination and underscore the environmental risks posed by commonly used disinfectants in driving the spread of clinically relevant multidrug-resistant pathogens.