Hydroxamate Siderophores Drive Persistent Free Radical Generation to Suppress Antibiotic Resistance Gene...

Composting agricultural waste is a cornerstone of circular agriculture but carries the risk of disseminating antibiotic resistance genes (ARGs). While persistent free radicals (PFRs) are known to continuously suppress ARGs, their natural yield in compost is often insufficient. Here, we demonstrate that hydroxamate siderophores (HDS) can capture Fe(III) to form stable redox-active complexes that act as potent electron shuttles, driving the generation of semiquinone radicals (SQ^•-) to inhibit ARG proliferation while promoting the humification process. In a 40 day cocomposting experiment with rice straw and pig manure, HDS amendment accelerated humification by 24.7% and enriched the quinone moieties within the humic matrix by 22.3%. HDS-Fe(III) complexes were predominantly reduced via microbial activity to HDS-Fe(II), which then served as a potent electron donor due to its significantly lowered redox potential. This drove spontaneous electron transfer to quinone moieties, increasing SQ^•- production by 2.1-7.4 times. The sustained oxidative pressure imposed by SQ^•- significantly inhibited plasmid-mediated conjugative transfer frequency by 65.3-84.4% via inducing membrane damage of critical host bacteria (such as Streptomyces). Consequently, mid- to high-risk ARGs in HDS-treated compost products were reduced by 11.6-26.6%. Application of HDS-treated compost products to paddy soil confirmed the persistent mitigation of ARG propagation risks. Overall, this HDS-based approach achieves the dual goals of compost valorization and biosafety, advancing the sustainability of circular agriculture within the "One Health" framework.