Neglected contributors to the transmission of bacterial antibiotic resistance in drinking water: Extracellular antibiotic resistance genes and the natural transformation.

Antibiotic resistance genes (ARGs) have increasingly gained recognition as an "emerging contaminant" that poses a threat to the biosafety of drinking water. However, previous researches have primarily focused on the intracellular state of ARGs and rarely investigated the ecological characteristics (e.g., distribution and origin), environmental behavior (spread), and risks of extracellular form (eARGs) within drinking water systems. Therefore, this review evaluated isolation strategies and extraction methods for recovering eARGs from drinking water, elucidated the distribution characteristics of eARGs, and examined their impact on the antibiotic resistome from source water to tap water. We emphasized that chlorination and biological treatments significantly contribute to the prevalence and persistence of eARGs in drinking water. Moreover, we highlighted the role of biological reactors (e.g., biofilter, biological activated carbon) and drinking water distribution systems in facilitating the natural transformation of eARGs while significantly contributing to bacterial antibiotic resistance (BAR) propagation. Finally, we summarized the current risk assessment systems for ARGs and critically address remaining challenging questions necessary for better forecasting health risks associated with eARGs in drinking water environments. Collectively, this review enhances the understanding of ecological characteristics and environmental behavior of eARGs in drinking water while providing important implications for controlling and reducing BAR contamination not only in drinking water but also in other aquatic environments.