Enterococcus niche formation in the GI tract

描述（由申请人提供）：肠道粘膜表面蕴藏着一个巨大而复杂的微生物生态系统，微生物组，它与宿主的发育和保护密切相关。粪肠球菌（Enterococcus faecalis， EF）是这一生态系统的成员之一，它是一种通常与宿主共生的“病原体”，但当肠道内稳态被破坏时，它也可以侵入宿主并引起全身性疾病。因此，它是一种理想的模式生物，可以在复杂的生态系统中用于探测细菌-宿主相互作用，这种相互作用有助于肠球菌在胃肠道中形成生态位。我们假设EF通过细菌和宿主之间复杂的相互作用在胃肠道中建立了它的生态位。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。我们将采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（Aim 1）。然后，我们将使用微阵列技术确定EF定殖和细菌素产生对宿主肠黏膜基因表达的影响。我们预计我们将确定几个微生物和宿主因素，这些因素对EF在胃肠道建立稳定定植的能力至关重要。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中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，这种相互作用允许这些多重抗生素耐药的医院获得性细菌持续在肠道定植，并为导致肠球菌易位和宿主全身感染的相互作用提供见解。

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.