Zang Zhiyu, Zhang Chengqian, Park Kyoung Jin, Schwartz Daniel A, Podicheti Ram, Lennon Jay T, Gerdt Joseph P
Department of Chemistry, Indiana University, Bloomington, IN, USA.
Department of Biology, Indiana University, Bloomington, IN, USA.
Nat Microbiol. 2025 Feb;10(2):362-373. doi: 10.1038/s41564-024-01910-8. Epub 2025 Jan 8.
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.
为了超越竞争对手,微生物会产生并分泌次生代谢产物,这些产物能够杀死邻近细胞并隔离营养物质。这种代谢物介导的竞争可能是在病毒病原体存在的复杂微生物群落中进化而来的。因此,我们推测微生物会分泌天然产物,使竞争对手对噬菌体感染敏感。我们使用二元相互作用筛选和化学表征来鉴定链霉菌属产生的一种次生代谢产物(天蓝色菌素),该产物在体外能使其土壤中的竞争对手枯草芽孢杆菌对噬菌体感染敏感。铁载体天蓝色菌素通过螯合铁使枯草芽孢杆菌对一组裂解性噬菌体(SPO1、SP10、SP50、Goe2)敏感,从而阻止了枯草芽孢杆菌静止期和芽孢形成的主要调节因子Spo0A的激活。代谢组学分析表明,其他细菌天然产物也可能为其生产者提供噬菌体介导的竞争优势。总的来说,这项工作揭示了天然产物与噬菌体之间的协同作用可以塑造微生物之间竞争的结果。