Fungal fusaric acid triggers a conserved siderophore-based defense strategy in Bacillus velezensis

Fusarium wilt, caused by the soil-borne fungal pathogen Fusarium oxysporum , leads to devastating yield losses in high-value crops such as tomato, cucumber, and watermelon. To develop effective and sustainable biocontrol strategies, a deeper understanding of how beneficial rhizobacteria counteract key fungal virulence factors is needed. Here, we report that the beneficial bacterium Bacillus velezensis exerts a siderophore-based defense mechanism against fusaric acid (FA), a major virulence metabolite produced by F. oxysporum . We show that FA inhibits the growth of susceptible bacteria by chelating iron and inducing iron starvation. In response, strain B31 responds to FA exposure, triggering transcriptional reprogramming and strongly upregulating the biosynthetic cluster for the siderophore bacillibactin. This results in enhanced bacillibactin production, which outcompetes FA for iron binding because of its higher affinity, thereby conferring innate resistance to the bacterium. Functionally, this iron-scavenging response not only restores bacterial fitness under FA stress but also enhances antifungal activity in vitro. Crucially, in plant assays, this mechanism mitigated FA-induced phytotoxicity and significantly improved plant protection against F. oxysporum infection. Notably, this FA-responsive siderophore defense pathway appears to be conserved among diverse B. velezensis strains, underscoring its ecological and evolutionary importance. Our study reveals a novel interkingdom signaling paradigm in which a beneficial bacterium coopts a fungal virulence factor to activate a protective iron-competition strategy, highlighting a sophisticated microbial adaptive response that enhances plant health in the rhizosphere.