Phthalates Promote Dissemination of Antibiotic Resistance Genes: An Overlooked Environmental Risk

Plastics-microorganism interactions have aroused growing environmental and ecological concerns. However, previous studies concentrated mainly on the direct interactions and paid little attention to the ecotoxicology effects of phthalates (PAEs), a common plastic additive that is continuously released and accumulates in the environment. Here, we provide insights into the impacts of PAEs on the dissemination of antibiotic resistance genes (ARGs) among environmental microorganisms. Dimethyl phthalate (DMP, a model PAE) at environmentally relevant concentrations (2-50 μg/L) significantly boosted the plasmid-mediated conjugation transfer of ARGs among intrageneric, intergeneric, and wastewater microbiota by up to 3.82, 4.96, and 4.77 times, respectively. The experimental and molecular dynamics simulation results unveil a strong interaction between the DMP molecules and phosphatidylcholine bilayer of the cell membrane, which lowers the membrane lipid fluidity and increases the membrane permeability to favor transfer of ARGs. In addition, the increased reactive oxygen species generation and conjugation-associated gene overexpression under DMP stress also contribute to the increased gene transfer. This study provides fundamental knowledge of the PAE-bacteria interactions to broaden our understanding of the environmental and ecological risks of plastics, especially in niches with colonized microbes, and to guide the control of ARG environmental spreading.