The multiple antimicrobial mechanisms mediated by microbial siderophores and their application prospects.

Siderophores are low-molecular-weight (<1500 Da) chelaters secreted by microorganisms under iron-limiting and bind ferric ions (Fe³⁺) with high affinity, supporting iron homeostasis, competition, and pathogenicity regulation. They are sythesized through the nonribosomal peptide synthetase (NRPS) and the NRPS-independent (NIS) pathway, and controlled by the Fur (ferric uptake regulator)-dependent regulation, then exported by the major facilitator superfamily (MFS), resistance-nodulation-division (RND), or ATP-binding cassette (ABC) family transport systems. After chelating iron, complexes are recognized by TonB-dependent receptors and transported into cells. Siderophores inhibit competitors by depriving iron, delivering toxic compounds into cells, and regulating virulence via quorum sensing. They also shape microbial community dynamics. Applications include siderophore antibiotic conjugates such as cefiderocol, receptor targeting, and agricultural biocontrol. Challenges remain in receptor redundancy, ecological complexity, and safety, and future work should integrate omics approaches to develop targeted antimicrobial strategies. Ultimately, siderophore-based strategies offer a promising paradigm shift from direct bactericidal action to resource restriction and virulence attenuation, potentially reducing selective pressure for resistance and opening new avenues for sustainable management of infectious diseases and agricultural pests.