Abstract
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.
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Acknowledgements
The study was supported financially by the National Natural Science Foundation of China (grants nos. 52322007 and 52321005), the Guangdong Basic and Applied Basic Research Foundation (no. 2023B1515020077), Shenzhen Science and Technology Program (nos. GXWD20231129112832001, JCYJ20240813105125034, and KCXFZ20240903092800002) and the State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology (no. 2024TS08). D.G.J.L. also thanks the Swedish Research Council VR (no. 2022-00945) and the Swedish State under an agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-965785), for financial support.
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L.-Y.Z. drafted the manuscript. B.L., D.G.J.L. and A.-J.W. conceptualized the Perspective, set the overall direction and framework, and helped to balance and refine the viewpoints. H.-L.C. proofread the manuscript and revised the language. Q.L., K.S. and S.-H.G. contributed to discussion of the content and provided comments and revision suggestions. All authors reviewed and approved the final version of the manuscript.
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Zhang, LY., Cui, HL., Li, Q. et al. Neglected positive role of inactivating antibiotic resistance genes in the environment.
Nat Water (2026). https://doi.org/10.1038/s44221-026-00640-x
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DOI: https://doi.org/10.1038/s44221-026-00640-x
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