Functional genomics analysis of colonization and persistence of Enterococcus faecalis in the gastrointestinal tract.

粪肠球菌在胃肠道中定植和持续存在的功能基因组学分析。

• 批准号: 9215645
• 负责人: GARY M DUNNY
• 金额: $ 49.47万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-04 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9215645
• 关键词: Animals; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Bacteria; Behavior; Bile fluid; Blood Circulation; Cell Wall; Cells; Complex; Development; Disease; Ecology; Enterococcus; Enterococcus faecalis; Enterococcus faecium; Exhibits; Gastrointestinal tract structure; Gene Cluster; Gene Expression; Genetic; Genetic Determinism; Genetic Screening; Genome; Genus staphylococcus; Germ-Free; Growth; Habitats; Healthcare; Heart Valves; Host Defense; Human; Impairment; Infection; Innate Immune System; Insecta; Intestines; Invaded; Laboratories; Lead; Libraries; Life; Life Style; Methods; Microbe; Microbial Biofilms; Microscopic; Microscopy; Minor; Modeling; Mus; Mutation; Nosocomial Infections; Opportunistic Infections; Organism; Pathogenicity; Pilum; Polysaccharides; Production; Proteins; Regulation; Research; Research Personnel; Resistance; Resolution; Role; Scanning Electron Microscopy; Site; Streptococcus; Study models; Surface; Symbiosis; Techniques; Urinary tract; Virulence; Work; antimicrobial drug; base; experimental study; fitness; follow-up; functional genomics; genome-wide; gut microbiota; humanized mouse; in vivo; interest; killings; member; microbial; microbial community; microbiome; mouse model; mutant; novel; pathogen; pressure; prevent; public health relevance; resistant strain; screening; tool; trait; transcription factor; virtual

 DESCRIPTION (provided by applicant): This project will examine the role of determinants encoded within the core genome of Enterococcus faecalis in adaptation to survival, growth, and persistence in the mammalian gastrointestinal tract. E. faecalis is a leading cause of hospital-acquired infections whose treatment is impeded by the inherent and acquired antibiotic resistance of the organism, and by its propensity to grow and survive in hostile conditions, and by its ability to transition between commensal and pathogenic lifestyles. Virtually all enterococcal infections are caused by organisms residing in the gut that escape to other body sites. It is well understood that antibiotic treatment or impairment of normal host defenses can result in overgrowth of enterococci in the intestine. However, we know very little about the inherent traits that allow the organism to establish in a healthy intestine, an essential prelude t enterococcal diseases. We will study the model laboratory strain OG1RF in both germ-free mice, and in "humanized" animals carrying a human-derived gut microbial community. We will use a powerful new genetic screen we have termed "Smart TnSeq" to identify genetic determinants encoding proteins and small regulatory RNAs that contribute to competitive fitness in the GI tract, and begin to study their functions and mechanisms of action. We will use high-resolution microscopic techniques to examine the behavior of the organisms in vivo, and the expression of genes of interest. The results of this research will include the following: 1) A genome-wide picture of the role of determinants of intestinal fitness will emerge. 2) We will have a much better understanding of preferred sites of colonization of enterococci, and how gene expression is regulated in these favored niches. 3) In the longer term, we may identify new ecologically based strategies, which could prevent enterococcal infections without necessarily killing the bacteria, reducing selection for resistance.

 描述（由应用程序提供）：该项目将研究粪肠球菌核心基因组中编码的确定词的作用，以适应哺乳动物胃肠道的生存，生长和持久性。粪肠球菌是医院获得感染的主要原因，其治疗受到生物体的继承和获得的抗生素耐药性的阻碍，以及它在敌对条件下生长和生存的能力，以及其在致病和致病生活之间过渡的能力。几乎所有的肠球菌感染都是由居住在肠道中的生物引起的。众所周知，抗生素治疗或正常宿主防御损害可能导致肠内肠球菌过度生长。但是，我们对允许生物体在健康的肠道中建立的继承性状知之甚少，这是一种必不可少的前奏肠球菌疾病。我们将研究两种无菌小鼠的模型实验室菌株OG1RF，以及带有人类源自肠道微生物群落的“人性化”动物。我们将使用称为“智能TNSEQ”的强大新遗传屏幕来识别编码蛋白质和小的调节性RNA的遗传确定剂，这些RNA有助于GI区域的竞争性适应性，并开始研究其作用的功能和机制。我们将使用高分辨率微观技术来检查体内生物体的行为以及感兴趣的基因的表达。这项研究的结果将包括以下内容：1）全基因组确定肠道适应性的作用的图片将出现。 2）我们将对肠球菌定植的首选位点有更好的了解，以及如何在这些受青睐的壁nike中调节基因表达。 3）从长远来看，我们可以确定新的基于生态的策略，这些策略可以防止肠球菌感染而无需杀死细菌，从而减少抗药性的选择。