Nitrate respiration by Salmonella during gut inflammation

描述(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和传播的极大兴趣。虽然抗生素耐药性显然可以促进新的致病克隆的扩大(例如，多重耐药的沙门氏菌血清型)，但关于加强新出现的病原体的持久性和传播的其他因素的信息仍然很少。哪些分子机制负责新的致病鼠伤寒沙门氏菌克隆的出现和传播，这是一个将在本申请中解决的高度影响的话题。我们的中心假设是，水平获得的III型分泌系统效应器Sope诱导宿主来源的硝酸盐的产生，这是一种具有高能量价值的电子受体，从而通过厌氧硝酸盐呼吸促进肠腔内沙门氏菌的繁殖。我们将通过追求以下具体目标来测试我们假设的关键方面：1)确定SOPE在传播成功中的作用和2.)确定SOPE在调节炎症肠道中涉及厌氧硝酸盐和四硫酸盐呼吸的基因表达中的作用。成功完成对胃肠炎研究有很大的影响，因为它提供了一个新的概念，即 沙门氏菌的进化可能是通过使新的营养物质，如无氧呼吸电子受体在炎症的肠道中可用来推动的，从而促进传播成功。

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.