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

 描述(申请人提供)：几乎所有入侵宿主的细菌都必须在最佳的位置和时间开启其入侵宿主所需的基因的表达，包括毒力基因，以获得最大的效果。这些细菌依靠它们的传感机制来检测宿主特有信号的存在，包括离子或pH的变化。我们最新的研究表明，一组47种细菌共享一种感知机制，即Exor-EXOS/ChvI(RSI)入侵开关，这一机制在苜蓿中华根瘤菌中被最好地理解。紫花苜蓿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。然而，紫花苜蓿RSI入侵开关的宿主特异性信号仍然未知。我们的长期目标是了解苜蓿及其相关病原菌如何感知宿主的存在，并创造方法来阻止或改变感知机制，以造福人类健康。我们目前的研究目标是确定紫花苜蓿RSI入侵开关的宿主特异性信号。我们最近的发现使我们将注意力集中在感染室中苜蓿链霉菌细胞的变化上，在那里，苜蓿链球菌发起了对宿主细胞的入侵。这个封闭的感染室是在卷曲的根毛内形成的，但在拓扑上形成在根毛之外。我们目前的假设是，植物的生长改变了根毛表面相对于周围土壤的离子浓度和pH值，这是由于离子在根毛内和根毛外的泵送。侵染室在拓扑上位于根毛之外，因此离子浓度和pH值将与土壤中的离子浓度和pH值发生类似的变化。这一假说得到了我们之前发表的关于RSI模型分子机制的工作的支持，我们的初步结果表明RSI开关参与了对离子变化的感知。我们建议1)确定RSI开关感测的离子变化，2)确定RSI感测离子变化的分子机制。这项研究的成功完成将表明细菌病原体可以检测到宿主表面独特的离子浓度，从而激活其毒力基因的表达，并为细菌分子离子传感机制提供深入的认识。由于所有生物都会吸收和分泌离子，我们的发现可能会影响对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.