A Periplasmic Global Regulator, ExoR,for Bacterial Invasion of Host Cells

 描述（由申请人提供）：几乎所有的宿主入侵细菌都必须在最佳地点和时间打开其宿主入侵所需的基因（包括毒力基因）的表达，以达到最大效果。这些细菌依靠它们的传感机制来检测宿主特异性信号的存在，包括离子或pH值的变化。我们最近的研究表明，一组47种细菌共享一种传感机制，即ExoR-ExoS/ChvI（RSI）入侵开关，这在苜蓿中华根瘤菌中得到了最好的理解。色葡萄苜蓿RSI入侵开关控制着数百个参与共生植物细胞入侵和生长的细菌基因的表达。S.然而，苜蓿RSI入侵开关仍然未知。我们的长期目标是了解S。草木樨及其相关的病原菌感知宿主的存在，并创造出阻断或改变感知机制的方法，以利于人类健康。我们目前的研究目标是确定宿主特异性信号的S。苜蓿RSI入侵开关。我们最近的研究结果使我们关注S.苜蓿根瘤菌细胞的感染室，其中S。草蛉开始入侵宿主细胞这种封闭的感染腔形成在卷曲的根毛内部，但在拓扑学上位于根毛外部。我们目前的假设是，植物生长改变离子浓度和pH值的根毛表面相对于周围的土壤，由于泵的离子进出根毛。侵染室在拓扑学上位于根毛外部，使得离子浓度和pH将与土壤中的离子浓度和pH类似地改变。这一假设是支持我们以前发表的工作的分子机制的RSI模型和我们的初步结果表明，RSI开关参与传感离子的变化。我们建议1）确定RSI开关感测的离子变化，以及2）确定控制离子变化的RSI感测的分子机制。该研究的成功完成将表明细菌病原体可以检测宿主表面的独特离子浓度，以激活其毒力基因的表达，并为细菌分子离子传感机制提供见解。由于所有生物体都能吸收和分泌离子，我们的发现可能会影响细菌宿主感知机制的研究。

 DESCRIPTION (provided by applicant): Almost all host-invading bacteria have to turn on the expression of their genes required for host invasion including virulence genes at the optimal place and time for maximum effect. These bacteria rely on their sensing mechanisms to detect the presence of host-specific signals, including ionic or pH changes. Our most recent study shows that a group of 47 bacteria share a sensing mechanism, the ExoR-ExoS/ChvI (RSI) invasion switch, which is best understood in Sinorhizobium meliloti. The S. meliloti RSI invasion switch controls the expression of hundreds of bacterial genes involved in invasion and growth in symbiotic plant cells. The host specific signals for the S. meliloti RSI invasion switch, however, remain unknown. Our long-term objective is to understand how S. meliloti and its related pathogenic bacteria sense the presence of a host and create ways to block or alter the sensing mechanism for the benefit of human health. Our current research objective is to identify the host specific signals for the S. meliloti RSI invasion switch. Our recent findings have led us to focus the changes of S. meliloti cells in the infection chamber, where S. meliloti launches their invasion of host cells. This enclosed infection chamber is formed inside a curled root hair but topologically outside the root hair. Our current hypothesis is that plant growth changes ionic concentrations and pH on the root hair surface relative to the surrounding soil due to the pumping of ions in and out of root hairs. The infection chamber is topologically outside the root hair so that ionic concentrations and pH will be similarly changed from those in the soil. This hypothesis is supported by our previously published work on the molecular mechanism of the RSI model and our preliminary results showing that the RSI switch is involved in sensing ionic changes. We propose to 1) determine the ionic changes sensed by the RSI switch, and 2) determine the molecular mechanism governing RSI sensing of ionic changes. The successful completion of the proposed research will show bacterial pathogens can detect unique ionic concentrations on host surface to activate the expression of their virulence genes and provide insights on the bacterial molecular ionic sensing mechanism. Since all living organisms take up and secrete ions, our findings could impact studies of bacterial host sensing mechanisms in general.