Nitrate respiration by Salmonella during gut inflammation

描述（由申请人提供）：最近新的细菌病原体的出现和传播引起了人们对传染病如何在宿主群体中持续存在和传播的极大兴趣。虽然很明显，抗生素耐药性可以促进新的致病性克隆（例如耐多药沙门氏菌血清型）的扩大，但关于增强新出现病原体持久性和传播的其他因素的信息仍然很少。哪些分子机制是负责一个新的致病性鼠伤寒沙门氏菌克隆的出现和传播的问题代表了一个高影响的主题，将在本应用程序中解决。我们的中心假设是，水平获得的III型分泌系统效应物SopE诱导宿主衍生的硝酸盐产生，这是一种能量价值很高的电子受体，从而通过厌氧硝酸盐呼吸促进肠道内沙门氏菌的繁殖。我们将通过追求以下具体目标来检验我们假设的关键方面：2.确定SopE在传输成功中的作用。确定SopE在调节炎症肠道中参与厌氧硝酸盐和四硫酸盐呼吸的基因表达中的作用。通过提供一个新概念，成功完成具有很强的潜力，对胃肠炎研究产生重大影响

DESCRIPTION (provided by applicant): The recent emergence and spread of new bacterial pathogens has generated great interest into how infectious diseases can persist and spread within host populations. Although it is clear that antibiotic resistance can contribute to the expansion of a new pathogenic clone (e.g. multi-drug resistant Salmonella serovars), information on other factors that enhance persistence and spread of emerging pathogens remains sparse. The question of which molecular mechanisms are responsible for the emergence and transmission of a new pathogenic S. Typhimurium clone represents a high-impact topic that will be addressed in this application. Our central hypothesis is that the horizontally acquired type III secretion system effector SopE induces production of host-derived nitrate, an energetically highly valuable electron acceptor, thus fueling a bloom of Salmonella in the gut lumen through anaerobic nitrate respiration. We will test key aspects of our hypothesis by pursuing the following specific aims: 1.) Determine the role of SopE on transmission success and 2.) Determine the role of SopE in modulating expression of genes involved in anaerobic nitrate and tetrathionate respiration in the inflamed gut. Successful completion has a strong potential to have a high impact on gastroenteritis research by providing a novel concept, i.e. that the evolution of Salmonella may be driven by making new nutrients such as anaerobic respiratory electron acceptors available in the inflamed gut, thus boosting transmission success.