Streptomyces secretes a siderophore that sensitizes competitor bacteria to phage infection

To overtake competitors, microbes produce and secrete secondary metabolites that kill neighbouring cells and sequester nutrients. This metabolite-mediated competition probably evolved in complex microbial communities in the presence of viral pathogens. We therefore hypothesized that microbes secrete natural products that make competitors sensitive to phage infection. We used a binary-interaction screen and chemical characterization to identify a secondary metabolite (coelichelin) produced by Streptomyces sp. that sensitizes its soil competitor Bacillus subtilis to phage infection in vitro. The siderophore coelichelin sensitized B. subtilis to a panel of lytic phages (SPO1, SP10, SP50, Goe2) via iron sequestration, which prevented the activation of B. subtilis Spo0A, the master regulator of the stationary phase and sporulation. Metabolomics analysis revealed that other bacterial natural products may also provide phage-mediated competitive advantages to their producers. Overall, this work reveals that synergy between natural products and phages can shape the outcomes of competition between microbes. A secondary metabolite sensitizes competitor Bacillus subtilis to a wide panel of lytic phages by sequestering iron and preventing the activation of Spo0A.