Where do the antibiotic resistance genes come from? A modulated analysis of sources and loads of resistances in Lake Maggiore

: Antibiotic resistance genes (ARGs) are abundant in aquatic ecosystems affected by human activities. Understanding the fate of ARGs across different ecosystems is essential because of the significant role aquatic environments play in the cycle of antibiotic resistance. We quantified selected ARGs in Lake Maggiore, its main tributaries, and the effluent of the main wastewater treatment plant (WWTP) discharging directly into the lake. We linked their dynamics to the different anthropogenic impacts in each tributary's watershed. The dynamics of tetA in the lake were influenced by those of the rivers and the WWTP effluent, and by the concentration of N-NH4, related to anthropogenic pollution, while sul2 abundance in the lake was not influenced by any water inflow. The dynamics of the different ARGs varied across the different rivers. Rivers with watersheds characterized by high population density, touristic activities, and secondary industries released more ARGs, while ermB correlated with higher numbers of primary industries. This study suggests a limited contribution of treated wastewater in the spread of ARGs, indicating as prevalent origin other sources of pollution, calling for a reconsideration on what are considered the major sources of ARGs into the environment.