Ferric Uptake Regulator Contributes to Pseudomonas donghuensis HYS-Induced Iron Metabolic Disruption in Caenorhabditis elegans

Iron is essential for vital biological processes, with its metabolism closely linked to host-pathogen interactions. <i>Pseudomonas donghuensis</i> HYS, with its superior iron uptake capacity, demonstrates pronounced virulence toward <i>Caenorhabditis elegans</i>. However, the virulence mechanisms remain unexplored. Ferric uptake regulator (Fur) regulates iron homeostasis and pathogenicity in bacteria, yet its role in HYS-mediated <i>C. elegans</i> pathogenesis requires systematic investigation. In this study, comparing the pathogenic processes of HYS and <i>P. aeruginosa</i> PA14 revealed that HYS causes stronger, irreversible toxicity via distinct mechanisms. Transcriptomics revealed that HYS infection disrupts <i>C. elegans</i> iron metabolism pathways, specifically iron transport, and iron-sulfur cluster utilization. Fur was identified as a pivotal regulator in HYS virulence and was indispensable for its colonization. Specifically, Fur was critical for disrupting nematode iron metabolism, as <i>fur</i> deletion eliminated this effect. While Fur regulated two HYS siderophores, neither of them mediated in the iron metabolism disruption of <i>C. elegans</i>. Screening identified Fur-regulated virulence factors to further investigate the function of Fur in HYS virulence, particularly alkaline proteases, and type II secretion system components. This study highlight that HYS can disrupt the iron metabolism pathway in <i>C. elegans</i>; Fur serves as a pivotal positive regulator in HYS-induced damage, particularly in disrupting iron metabolism through a siderophore-independent pathway. These findings expand the understanding of <i>Pseudomonas</i> pathogenicity and Fur-mediated virulence regulation.