Probiotic paradox: bacillibactin from <i>Bacillus velezensis</i> drives pathogenic <i>Vibrio alginolyticus</i> proliferation through siderophore piracy

The opportunistic pathogen <i>Vibrio alginolyticus</i> dominates iron-depleted marine ecosystems, likely driven by its diverse repertoire of siderophore receptors that enable iron piracy from exogenous sources. While the ability to utilize xenosiderophores via piracy can be advantageous under iron limitation, the identities of exogenous siderophore producers interacting with <i>V. alginolyticus</i> remain poorly characterized. Here, we show that 17.0% of siderophore-producing isolates from <i>V. alginolyticus</i>-dominated mariculture systems significantly enhance the growth of <i>V. alginolyticus</i> HN08155 under iron limitation, including six <i>Bacillus</i> strains established as probiotics in aquaculture. Notably, <i>Bacillus velezensis</i> WD26-16 exhibits the strongest growth-promoting effect via catechol-type siderophore bacillibactin production. Genomic analyses demonstrate that 86.1% of marine <i>Bacillus</i> spp. in the Genome Taxonomy Database harbor conserved bacillibactin biosynthetic gene clusters, with near-complete conservation across all <i>B. velezensis</i> strains, suggesting ubiquitous siderophore-mediated interaction with <i>V. alginolyticus</i>. Exogenous bacillibactin induces distinct metabolic modulation in <i>V. alginolyticus</i>, activating pathways critical for amino acid metabolism, protein biosynthesis, and energy production to sustain proliferative demands. This metabolic adaptation is mediated by coordinated upregulation of multiple siderophore receptors (IutA, IrgA, VctA) that allows functional plasticity in xenosiderophore piracy. Co-culture experiments reveal that <i>V. alginolyticus</i> exploits bacillibactin to outcompete <i>B. velezensis</i> and achieves a 3.4-fold growth advantage compared to the monoculture. Our results uncover an ecological paradox: probiotic <i>B. velezensis</i> inadvertently enhances pathogenic <i>V. alginolyticus</i> proliferation through siderophore piracy. This iron-centric competition mechanism likely drives vibriosis outbreaks in aquaculture systems, necessitating urgent reassessment of probiotic selection criteria to avoid unintended pathogen amplification.