Luo Youqing, Srinivas Apsara, Guidry Casey, Bull Carolee, Haney Cara H, Hamilton Corri
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
mSphere. 2025 Sep 30;10(9):e0027725. doi: 10.1128/msphere.00277-25. Epub 2025 Sep 8.
Through horizontal gene transfer, closely related bacterial strains assimilate distinct sets of genes, resulting in significantly varied lifestyles. However, it remains unclear how strains properly regulate horizontally transferred virulence genes. We hypothesized that strains may use components of the core genome to regulate diverse horizontally acquired genes. To investigate how closely related bacteria assimilate and activate horizontally acquired DNA, we used a model consisting of strains in the // (BCM) subclade , including species N2E2 and N2C3, which exhibit contrasting lifestyles on the model plant sp. N2E2 is a plant commensal and contains genes encoding biosynthetic enzymes for the antifungal compound 2,4-diacetylphloroglucinol (DAPG). In contrast, sp. N2C3 lacks DAPG biosynthesis and has gained a pathogenic island encoding syringomycin (SYR)- and syringopeptin (SYP)-like toxins from the plant pathogen . This causes a transition in lifestyle from plant-protective N2E2 to plant-pathogenic N2C3. We found that N2E2 and N2C3 share a highly conserved two-component system GacA/S, a known regulator of DAPG and SYR/SYP. Using knockout mutations, we found that a mutation resulted in loss of expression of SYR/SYP virulence genes and returned pathogenic N2C3 to a plant commensal lifestyle. Our study further explored the conservation of regulatory control across strains by demonstrating that GacA genes from both distant and closely related strains could functionally complement one another across the genus.IMPORTANCEEmerging pathogens represent a significant threat to humans, agriculture, and natural ecosystems. Bacterial horizontal gene transfer (HGT) aids in the acquisition of novel genes that facilitate adaptation to new environments. Our work shows a novel role for GacA in orchestrating the regulatory changes necessary for virulence and lifestyle transitions facilitated by HGT. These findings suggest that the GacA/S system plays a key role in mediating transitions across diverse symbiotic lifestyles. This work provides insights into the mechanisms that drive the emergence of pathogenic strains and highlights potential targets for managing bacterial threats to plant health.
通过水平基因转移，亲缘关系密切的细菌菌株会吸收不同的基因集，从而导致生活方式显著不同。然而，目前尚不清楚菌株如何恰当地调控水平转移的毒力基因。我们推测，菌株可能利用核心基因组的组分来调控多种水平获得的基因。为了研究亲缘关系密切的细菌如何吸收和激活水平获得的DNA，我们使用了一个模型，该模型由//（BCM）亚分支中的菌株组成，包括物种N2E2和N2C3，它们在模式植物sp.上表现出截然不同的生活方式。N2E2是一种植物共生菌，含有编码抗真菌化合物2,4-二乙酰基间苯三酚（DAPG）生物合成酶的基因。相比之下，sp. N2C3缺乏DAPG生物合成能力，并且从植物病原体中获得了一个编码丁香霉素（SYR）和丁香肽（SYP）样毒素的致病岛。这导致了生活方式从植物保护型的N2E2转变为植物致病型的N2C3。我们发现N2E2和N2C3共享一个高度保守的双组分系统GacA/S，这是一种已知的DAPG和SYR/SYP调节剂。通过基因敲除突变，我们发现一个突变导致SYR/SYP毒力基因表达丧失，并使致病的N2C3恢复到植物共生生活方式。我们的研究通过证明来自远缘和近缘菌株的GacA基因在整个属中能够在功能上相互补充，进一步探索了不同菌株间调控控制的保守性。重要性新兴病原体对人类、农业和自然生态系统构成重大威胁。细菌水平基因转移（HGT）有助于获取促进适应新环境的新基因。我们的工作显示了GacA在协调HGT促进的毒力和生活方式转变所需的调控变化方面的新作用。这些发现表明，GacA/S系统在介导不同共生生活方式的转变中起关键作用。这项工作深入了解了驱动致病菌株出现的机制，并突出了管理细菌对植物健康威胁的潜在靶点。
