Project description:Background Streptomyces are key contributors to soil microbiome function, known for their biosynthetic diversity. While advances in -omics technologies have improved our understanding of microbiome composition and metabolic potential, the mechanisms underpinning interspecies interactions remain poorly resolved. Here, we investigate the molecular basis of interactions among four sympatric Streptomyces soil microbiome isolates, focusing on phenotypic, metabolomic and transcriptomic responses. Results Co-culture experiments revealed that one isolate, strain A, exhibited pronounced phenotypic changes when grown alongside each of the other three strains. Untargeted metabolomics and RNA-seq analyses showed that strain A undergoes distinct metabolic and transcriptional shifts depending on its partner, with the strongest response elicited by strain C. Despite all four strains possessing a conserved desferrioxamine biosynthetic gene cluster, only strain C constitutively produced desferrioxamine B (DFO-B), a hydroxymate siderophore, indicating a role of iron bioavailability in the interaction. Supplementation with DFO-B or iron mimicked the growth stimulation of strain A observed in co-culture with strain C, and CRISPR base editing of desD in strain C abolished both DFO production and the phenotypic induction of strain A. However, transcriptomic profiles of strain A varied significantly depending on the partner strain, with distinct sets of biosynthetic gene clusters and metabolic pathways activated in response to strains B and C, suggesting additional cues beyond DFO-B. In contrast, strain D did not elicit growth stimulation in its partners, and itself showed downregulation of amino acid and carbon metabolism when co-cultured with strain C. These findings indicate that Streptomyces interactions are not only mediated by siderophore piracy but also involve complex, strain-specific molecular responses. Conclusions Our findings demonstrate that Streptomyces interactions are highly strain-specific and only partly mediated by siderophore piracy, with DFO-B acting as a potent interspecies cue. The divergent molecular responses to different partners suggest nuanced mechanisms of microbial sensing and competition. These insights advance our understanding of microbial crosstalk and highlight the ecological and evolutionary complexity of siderophore-mediated interactions. By integrating transcriptomics, metabolomics, and biochemical assays, we present a robust framework for dissecting microbial interactions, with implications for microbiome engineering and synthetic community design.
Project description:AMP-activated protein kinase (AMPK) stabilizes tubular cell metabolism and protects against renal fibrosis through promoting autophagy and mitochondrial homeostasis. Liver kinase B1 (LKB1) is the key regulator for AMPK activation. However, the direct activators of LKB1 are scarce in commercial. In this study, we report a novel LKB1 activator, the piericidin analogue S14 (PA-S14), which was isolated from the culture broth of a marine-derived Streptomyces strain by our group. PA-S14 binds with residue D176 in LKB1 kinase domain, and then induces LKB1 phosphorylated activation and its complex formation with MO25 and STRADα. Furthermore, PA-S14 promotes AMPK activation to enhance LC3B-II/LC3B-I ratio, trigger autophagosome formation and increase autophagic flux. PA-S14 exhibits perfect protective effects on stabilizing mitochondrial homeostasis, inhibiting tubular cell senescence, and retarding fibrogenesis in various CKD models (UUO, UIRI and adriamycin nephropathy models) and TGF-β-stimulated tubular cell culture. Transcriptomics sequencing and site-specific mutation analysis further prove that PA-S14 is a novel lead compound of LKB1 activator, which perfectly protects against renal fibrosis through inducing AMPK-mediated autophagy and mitochondrial homeostasis.
Project description:AMP-activated protein kinase (AMPK) stabilizes tubular cell metabolism and protects against renal fibrosis through promoting autophagy and mitochondrial homeostasis. Liver kinase B1 (LKB1) is the key regulator for AMPK activation. However, the direct activators of LKB1 are scarce in commercial. In this study, we report a novel LKB1 activator, the piericidin analogue S14 (PA-S14), which was isolated from the culture broth of a marine-derived Streptomyces strain by our group. PA-S14 binds with residue D176 in LKB1 kinase domain, and then induces LKB1 phosphorylated activation and its complex formation with MO25 and STRADα. Furthermore, PA-S14 promotes AMPK activation to enhance LC3B-II/LC3B-I ratio, trigger autophagosome formation and increase autophagic flux. PA-S14 exhibits perfect protective effects on stabilizing mitochondrial homeostasis, inhibiting tubular cell senescence, and retarding fibrogenesis in various CKD models (UUO, UIRI and adriamycin nephropathy models) and TGF-β-stimulated tubular cell culture. Transcriptomics sequencing and site-specific mutation analysis further prove that PA-S14 is a novel lead compound of LKB1 activator, which perfectly protects against renal fibrosis through inducing AMPK-mediated autophagy and mitochondrial homeostasis.
Project description:In this study, we describe the isolation and identification of Streptomyces isolates collected from traditional medicinal plants’ rhizosphere during a campaign in Hamedan Province, Iran. Traditional medicinal plants represent a rich and unique source for the isolation of Streptomyces and new antimicrobial compounds. This strain was isolated from the rhizosphere of Helichrysum rubicundum
Project description:To identify unique gene expression in cAMP supplemented Streptomyces coelicolor M145 strain. The genes with different gene expression might be key genes to understand the effects of cAMP supplementation on the transcriptome of Streptomyces coelicolor M145.
Project description:To identify unique gene expression in cAMP supplemented Streptomyces coelicolor M1146 strain. The genes with different gene expression might be key genes to understand the effects of cAMP supplementation on the transcriptome of Streptomyces coelicolor M1146.