Breaking the Pharmaceutical-ARG Nexus in Wastewater: Mechanistic Insights into Risk Mitigation by a Novel...

Wastewater treatment plants (WWTPs) serve as critical reservoirs and dissemination hotspots for pharmaceuticals and antibiotic resistance genes (ARGs), posing significant threats to environmental and public health. In this study, a novel riboflavin/ultraviolet/peracetic acid (RF/UV/PAA) disinfection process was developed to enhance the removal of these emerging contaminants. The process achieved superior performance in degrading 29 pharmaceuticals and eliminating 106 ARGs and 13 mobile genetic elements (MGEs), attributed to the action of both radical and non-radical species. The underlying risk mitigation potential was further elucidated through multiomics analyses. The results revealed that the RF/UV/PAA process suppresses ARG dissemination through a triple-mechanism pathway, directly inactivating host bacteria; blocking vertical gene transfer; enhancing pharmaceutical removal, which alleviates the selection pressure for resistance; and disrupting horizontal gene transfer (HGT) through MGE destruction and alterations in membrane permeability, extracellular polymeric substance secretion, adenosine triphosphate synthesis, and cellular motility. Notably, our results also suggest that non-antibiotic pharmaceuticals promote the MGE-mediated HGT of ARGs, challenging the conventional antibiotic-centric paradigm. This study not only establishes RF/UV/PAA disinfection as an effective technology for the synergistic removal of pharmaceuticals and ARGs in wastewater but also provides critical mechanistic insights to mitigate ARG dissemination via WWTP effluents.