Microbiome Composition Modulates Secondary Metabolism in a Multispecies Bacterial Community

Bacterial secondary metabolites are a major source of antibiotics and other bioactive compounds. In microbial communities, these molecules can mediate interspecies interactions and responses to environmental change. Despite the importance of secondary metabolites in human health and microbial ecology, little is known about their roles and regulation in the context of multispecies communities. In a simplified model of the rhizosphere composed of , , and , we show that the dynamics of secondary metabolism depend on community species composition and interspecies interactions. Comparative metatranscriptomics and metametabolomics reveal that the abundance of transcripts of biosynthetic gene clusters (BGCs) and metabolomic molecular features differ between monocultures or dual cultures and a tripartite community. In both two- and three-member cocultures, modified expression of BGCs for zwittermicin, petrobactin, and other secondary metabolites in and whereas the BGC transcriptional response to the community in itself was minimal. Pairwise and tripartite cocultures with displayed unique molecular features that appear to be derivatives of lokisin, suggesting metabolic handoffs between species. Deleting the BGC for koreenceine, another metabolite, altered transcript and metabolite profiles across the community, including substantial up-regulation of the petrobactin and bacillibactin BGCs in , suggesting that koreenceine represses siderophore production. Results from this model community show that bacterial BGC expression and chemical output depend on the identity and biosynthetic capacity of coculture partners, suggesting community composition and microbiome interactions may shape the regulation of secondary metabolism in nature.