Enterococcus niche formation in the GI tract

描述(由申请人提供)：肠粘膜表面包含一个巨大的复杂的微生物生态系统，微生物组，它与宿主的发展和保护密切相关。这个生态系统的成员之一是粪肠球菌(EF)，这是一种通常与宿主共生的“病原体”，但当肠道内环境平衡被破坏时，也会入侵宿主并导致全身疾病。因此，它是一种理想的模式生物，可用于复杂的生态系统中，以探索细菌与宿主之间的相互作用，这些相互作用有助于肠球菌在胃肠道内形成生态位。我们假设EF通过细菌和宿主之间的复杂相互作用在胃肠道建立了它的生态位。为了研究宿主对细菌的影响以及细菌对宿主的影响，我们将使用一种新的小鼠肠道EF定植模型。我们将使用基于重组酶的体内表达技术(RIVET)来研究宿主肠道环境对EF的影响(目标1)。然后，我们将利用微阵列技术，确定EF定植和细菌素生产对宿主肠道粘膜基因表达的影响。我们预计，我们将确定几个微生物和宿主因素，这些因素对于EF建立稳定的胃肠道定植能力至关重要。有了这些知识，我们将开始对细菌和宿主基因进行具体分析，以确定它们在胃肠道EF生态位形成过程中的作用。最终，这些发现将有助于更好地理解复杂的细菌-宿主相互作用，这些复杂的细菌-宿主相互作用使这些多重耐药的医院获得性细菌能够持续在肠道定植，并提供对导致肠球菌易位和宿主系统性感染的相互作用的洞察。 与公共卫生相关：胃肠道被数以万亿计的细菌定植，这些细菌对健康和疾病具有重要作用。其中一种细菌，粪肠球菌，当它从胃肠道传播时，可以导致住院患者的严重疾病，因为它是 对许多抗生素都有抗药性。这些研究的目标是了解通常在肠道和宿主中发现的细菌是如何相互作用的，从而允许细菌定植但防止感染。最终，通过了解粪肠球菌和胃肠道之间相互作用的机制，我们将开发新的方法来操纵这种相互作用，以利于个人健康和预防疾病。

DESCRIPTION (provided by applicant): Intestinal mucosal surfaces harbor a vast complex microbial ecosystem, the microbiome, which is intimately involved in host development and protection. One member of this ecosystem is Enterococcus faecalis (EF), a "pathobiont" that normally lives symbiotically with its host, but also can invade the host and cause systemic disease when intestinal homeostasis is disrupted. It is therefore an ideal model organism that can be used in a complex ecosystem to probe bacterial-host interactions that contribute to enterococcal niche formation in the GI tract. We hypothesize that EF establishes its niche in the GI tract through complex interactions between the bacterium and host. To investigate the host effect on the bacterium and the bacterium effect on the host we will use a novel mouse model for intestinal EF colonization. We will employ recombinase-based in vivo expression technology (RIVET) to investigate the impact of the host intestinal environment on EF (Aim 1). We will then determine the impact of EF colonization and bacteriocin production on host intestinal mucosal gene expression, using microarray technology. We anticipate that we will identify several microbial and host factors that are essential for EF's ability to establish stable colonization of he GI tract. With this knowledge we will begin to carry out specific analyses of both bacterial and host genes to determine their role in the process of EF niche formation in the GI tract. Ultimately, these findings will lead to a greater understanding of the complex bacterial-host interactions that allow persistent intestinal colonization by these multi-antibiotic resistant hospital-acquired bacteria, and offer insight into the interactions that result in enterococcal translocation and host systemic infection. PUBLIC HEALTH RELEVANCE: The gastrointestinal tract is colonized by trillions of bacteria that have an important role in health and disease. One of these bacteria, Enterococcus faecalis, can cause serious illness in hospitalized patients when it spreads from the GI tract, because it is resistant to many antibiotics. The goal of these studies is to understand how bacteria that are normally found in the intestinal tract and the host interact with each other to allow bacterial colonization but prevent infection. Ultimately, by understanding the mechanisms involved in the interaction between Enterococcus faecalis and the GI tract, we will develop new approaches for manipulating this interaction to benefit individual health and prevent disease.