Regulation of the Sinorhizobium meliloti ExoS/ChvI signaling pathway critical for host infection

项目摘要/摘要 许多α-变形菌侵入真核宿主的细胞，具有致病或有益的结果。示例 这种α-变形菌是人类病原体布鲁氏菌和巴尔通体以及植物共生体 中华根瘤菌值得注意的是，尽管这些α-变形菌在不同宿主中靶向不同的细胞类型， 它们都需要一个保守的细菌双组分信号通路来成功地与宿主相互作用： 布鲁氏菌中的BvrS/BvrR、巴尔通体中的BatS/BatR和中华根瘤菌中的ExoS/ChvI。突变细菌缺乏 该途径不能侵入宿主细胞，并表现出多效性表型，例如改变的细胞包膜功能。 然而，这些缺陷背后的分子机制尚未得到很好的理解。为了阐明 这个保守的信号通路的关键作用，该项目的重点是ExoS/ChvI信号通路， 苜蓿中华根瘤菌，一种研究与真核宿主相互作用的模式α-变形菌。最近的一 一项全基因组研究在S.苜蓿草。这项建议 从这项研究中建立，并使用分子遗传学方法来阐明这种保守的关键功能， 调控途径该项目的具体目标是：（1）鉴定直接受 ExoS/ChvI，（2）鉴定ExoS/ChvI的调控输入，和（3）表征 ExoS/ChvI.这项研究将提供深入了解的功能控制这一重要的信号通路 在主机交互过程中。此外，该项目还将提供宝贵的生物医学研究培训， 本科生和硕士生，包括那些来自生物医学研究中代表性不足的群体的学生 careers.

PROJECT SUMMARY/ABSTRACT Many alpha-proteobacteria invade cells of eukaryotic hosts with pathogenic or beneficial outcomes. Examples of such alpha-proteobacteria are the human pathogens Brucella and Bartonella and the plant symbiont Sinorhizobium. Remarkably, although these alpha-proteobacteria target different cell types in different hosts, they all require a conserved bacterial two-component signaling pathway for successful host interaction: BvrS/BvrR in Brucella, BatS/BatR in Bartonella, and ExoS/ChvI in Sinorhizobium. Mutant bacteria deficient in this pathway fail to invade host cells and exhibit pleiotropic phenotypes such as altered cell envelope function. However, the molecular mechanisms underlying these defects are not well understood. Toward elucidating the crucial roles of this conserved signaling pathway, this project focuses on the ExoS/ChvI signaling pathway of Sinorhizobium meliloti, a model alpha-proteobacterium for studying interactions with eukaryotic hosts. A recent genome-wide study identified 64 protein-encoding genes in the ExoS/ChvI regulon of S. meliloti. This proposal builds from that study and uses molecular genetic approaches to clarify the critical functions of this conserved regulatory pathway. Specific aims of the project are to: (1) Identify small RNA genes directly regulated by ExoS/ChvI, (2) Identify regulatory inputs to ExoS/ChvI, and (3) Characterize transcriptional target genes of ExoS/ChvI. This study will provide insight into the functions controlled by this important signaling pathway during host interaction. In addition, the project will provide valuable biomedical research training to undergraduate and master’s students, including those from groups underrepresented in biomedical research careers.