Enterococcus niche formation in the GI tract

胃肠道中肠球菌生态位的形成

• 批准号: 8494555
• 负责人: CHRISTOPHER J KRISTICH
• 金额: $ 17.98万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8494555
• 关键词: Animal Model; Animals; Antibiotic Resistance; Antibiotics; Bacteria; Cecum; Complex; Development; Disease; Ecosystem; Enterococcus; Enterococcus faecalis; Environment; Epithelial; Gastrointestinal tract structure; Gene Chips; Gene Expression; Gene Expression Profiling; Gene Targeting; Genes; Genetic Transcription; Goals; Health; Hospitals; Immune response; Individual; Infection; Infection prevention; Integration Host Factors; Intestines; Invaded; Knowledge; Large Intestine; Lead; Libraries; Microarray Analysis; Modeling; Multi-Drug Resistance; Mus; Nosocomial Infections; Organism; Patients; Process; Production; Proteins; RNA; Reporter; Resistance; Role; Site; Small Intestines; Stomach; Surface; Systemic disease; Systemic infection; Technology; Tissues; Vancomycin resistant enterococcus; Virulence Factors; bacteriocin; base; in vivo; insight; intestinal epithelium; intestinal homeostasis; member; microbial; microbial host; microbiome; mouse model; mutant; novel; novel strategies; prevent; promoter; recombinase; research study; response

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.

描述（由申请方提供）：肠粘膜表面含有大量复杂的微生物生态系统，即微生物组，其密切参与宿主发育和保护。粪肠球菌（Enterococcus faecalis，EF）是该生态系统的一个成员，它是一种“致病菌”，通常与宿主共生，但当肠道内稳态被破坏时，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，可用于在复杂的生态系统中探测细菌-宿主相互作用，有助于肠球菌在胃肠道中的生态位形成。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其生态位。为了研究宿主对细菌的影响和细菌对宿主的影响，我们将使用一种新的肠道EF定殖小鼠模型。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（目的1）。然后，我们将确定EF定植和细菌素生产对宿主肠粘膜基因表达的影响，使用微阵列技术。我们预计，我们将确定几个微生物和宿主的因素，是必不可少的EF的能力，建立稳定的殖民地的胃肠道。有了这些知识，我们将开始对细菌和宿主基因进行特异性分析，以确定它们在胃肠道EF生态位形成过程中的作用。最终，这些发现将导致对复杂的细菌-宿主相互作用的更深入了解，这些细菌-宿主相互作用允许这些多抗生素耐药的医院获得性细菌在肠道内持续定植，并深入了解导致肠球菌易位和宿主全身感染的相互作用。