Sodium bioenergetics in Yersinia pestis

项目主任/首席调查员(最后、第一、中间)：Hase，Claudia C.1R21 AI064190-01A2 所有活细胞都在初级离子泵的帮助下建立跨膜电化学梯度。已在许多微生物中发现了初级Na+泵，Na+离子的跨膜循环可能在几种病原菌的生理中起着重要作用。病原菌暴露在宿主内外的广泛环境中，必须能够适应周围组织的变化才能确定感染。尽管人们对能量的钠循环在鼠疫耶尔森氏菌感染过程中的作用知之甚少，但这种生物基因组中几个钠依赖系统的存在强烈表明，这种生物至少部分的能量代谢依赖于钠生物能量学。我们先前假设，细菌钠泵参与pH和钠稳态对细菌毒力是重要的，因此应该为开发新的干预策略提供一个靶点。事实上，我们的初步结果表明，在动物感染模型中，鼠疫杆菌的主要钠/质子逆向转运体(NhaA)突变株的毒力显著下降。这项应用的目的是在不同的实验检测中进一步确定钠生物能量学对鼠疫杆菌生理和毒力的贡献。我们将结合广泛的遗传操作和不同的生物能量学测量，研究不同的钠泵在鼠疫杆菌膜能量学中的作用。此外，我们将在体外和体内分析这些突变株的毒力特征，以更好地了解这些钠泵在不同阶段的重要性。 感染。 钠生物能量学可能在鼠疫杆菌生命周期的所有不同阶段都发挥着作用。因此，拟议的研究结果将对理解不同宿主管腔内与鼠疫菌生态学相关的基本生物学概念具有价值。因此，它提供了巨大的应用潜力，并将引起研究界广大受众的兴趣。

Program Director/Principal Investigator (Last, First, Middle): Hase, Claudia C. 1R21 AI064190-01A2 All living cells establish transmembrane electrochemical gradients with the help of primary ion pumps. Primary Na+ pumps have been discovered in many microorganisms and a transmembrane circulation of Na+ ions may play a significant role in the physiology of several pathogenic bacteria. Pathogenic bacteria are exposed to a wide range of environments both within and outside the host and have to be able to adapt to changes in the surrounding tissue to establish an infection. Although little is known about the role of the sodium cycle of energy during infection by Yersinia pestis, the presence of several sodium-dependent systems in the genome of this organism strongly suggests that this organism relies on sodium bioenergetics for at least part of its energy metabolism. We have previously hypothesized that bacterial sodium pumps involved in pH and sodium homeostasis are important for bacterial virulence and thus should provide a target for the development of a novel intervention strategy. Indeed, our preliminary results demonstrated a dramatic loss of virulence in the main sodium/proton antiporter (NhaA) mutant of Y. pestis in an animal infection model. The objectives of this application are to further define the contribution of sodium bioenergetics to Y. pestis physiology and virulence in different experimental assays. We will examine the roles of the different sodium pumps in the membrane energetics of Y. pestis by combining extensive genetic manipulations with various bioenergetic measurements. Furthermore, we will analyze the virulence traits of these mutants in vitro and in vivo to better understand the importance of these sodium pumps during the different stages of infection. Sodium bioenergetics probably plays a role in all of the various phases of the Y. pestis life cycle. Thus, the outcome of the proposed research will be of value to understanding fundamental biological concepts related to Y. pestis ecology in the lumen of its different hosts. It therefore offers great potential for application and will be of interest to a wide audience within the research community.