Siderophore systems at play: system interactions as drivers of diversification in pathogenic <i>Vibrio</i>

Iron acquisition is critical for bacterial survival and virulence, especially under the iron-limited conditions encountered in host environments. This study uncovers unexpected siderophore diversification within the piscibactin pathway, including two novel catecholate analogs and fluorinated derivatives produced via precursor-directed biosynthesis. We identify Irp5 as a versatile salicylate-activating enzyme that drives this metabolic flexibility. Moreover, the piscibactin and vanchrobactin systems interact at both biosynthetic and uptake levels, forming a resilient and adaptable iron acquisition network that supports virulence. These findings advance our understanding of siderophore-mediated iron acquisition and illustrate how enzymatic promiscuity and system interplay can be leveraged for synthetic biology and antimicrobial development. Given the widespread distribution of <i>irp</i>-HPI in <i>Vibrionaceae</i>, including human pathogens, our study provides a foundation for the rational design of antimicrobial strategies.