Neglected positive role of inactivating antibiotic resistance genes in the environment

Water environments serve as critical sources and conduits for antimicrobial resistance (AMR). The complex water cycle facilitates the transmission of antibiotics, resistant bacteria and resistance genes that have been released through anthropogenic activities, thereby reshaping AMR dynamics across different environmental compartments. Among these resistance determinants, inactivating antibiotic resistance genes (inactivating ARGs) encode enzymes that degrade or modify antibiotics to reduce their bioactivity. They play a complex and dual role bridging environmental reservoirs and clinical risk. While they can threaten the therapeutic effectiveness of antibiotics when transferred horizontally to pathogens, they also act as cooperative traits that lower local concentrations of bioactive antibiotics and relax selection for resistance. In turn, reduced antibiotic exposure can enhance ecosystem functions and stability in both host-associated and environmental microbiomes through ecosystem resilience and community protection. Inactivating ARGs represent a crucial intersection between AMR challenges and microbial community stability. Here we discuss the risks and ecological benefits of inactivating ARGs, and present intervention strategies aiming to both protect ecological resilience and limit resistance development in pathogens.