Probiotic paradox: bacillibactin from Bacillus velezensis drives pathogenic Vibrio alginolyticus proliferation through siderophore piracy

益生菌悖论:来自贝莱斯芽孢杆菌的芽孢杆菌素通过铁载体劫持促进致病性溶藻弧菌的增殖

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Abstract

The opportunistic pathogen Vibrio alginolyticus 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 V. alginolyticus remain poorly characterized. Here, we show that 17.0% of siderophore-producing isolates from V. alginolyticus-dominated mariculture systems significantly enhance the growth of V. alginolyticus HN08155 under iron limitation, including six Bacillus strains established as probiotics in aquaculture. Notably, Bacillus velezensis WD26-16 exhibits the strongest growth-promoting effect via catechol-type siderophore bacillibactin production. Genomic analyses demonstrate that 86.1% of marine Bacillus spp. in the Genome Taxonomy Database harbor conserved bacillibactin biosynthetic gene clusters, with near-complete conservation across all B. velezensis strains, suggesting ubiquitous siderophore-mediated interaction with V. alginolyticus. Exogenous bacillibactin induces distinct metabolic modulation in V. alginolyticus, 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 V. alginolyticus exploits bacillibactin to outcompete B. velezensis and achieves a 3.4-fold growth advantage compared to the monoculture. Our results uncover an ecological paradox: probiotic B. velezensis inadvertently enhances pathogenic V. alginolyticus 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.

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