Genomic Comparison of Infectious Strains E. Faecalis

传染性粪肠球菌菌株的基因组比较

• 批准号: 6907914
• 负责人: GEORGE M WEINSTOCK
• 金额: $ 22.01万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6907914
• 关键词: Enterococcus; bacteria infection mechanism; bacterial disease; bacterial genetics; computational biology; gene expression; gene mutation; genetic mapping; genetic strain; genome; method development; microarray technology; molecular biology information system; molecular cloning; polymerase chain reaction; single nucleotide polymorphism; virulence

DESCRIPTION (provided by applicant): Enterococcus faecalis is an important nosocomial pathogen. While a component of the normal human intestinal flora, E. faecalis is a low virulence organism. Yet a variety of infections by E. faecalis occur, including endocarditis, bacteremia, and infections of the urinary track and other tissues. The E. faecalis strains that cause these infections may differ in virulence factors from the docile strains that inhabit the healthy human intestine. Thus an important challenge is to determine the genetic differences between E. faecalis strains with different phenotypes. As a first step toward this goal, this project will determine the genomic sequences of two strains of Enterococcus faecalis, strains OG1RF and HH22, and compare them to the sequence of strain V583, the only other complete E. faecalis genomic sequence. Strain OG1RF is the major experimental strain of E. faecalis, used widely in research for many years, and on which much of the knowledge of E. faecalis biology is based. Strain HH22 is a closer relative of V583, but shows 100-fold greater infectivity in a mouse model. Comparison of these three genomes should provide information as to E. faecalis virulence as well as develop the methodology that can be applied to a wider ranger of strains. Two novel technologies will be used in this study. In the sequencing phase, high genome coverage using the pyrosequencing methodology of 454 Life Sciences will be aimed at reducing the amount of activity needed to bring the genome to a high quality finished grade. Once the sequences are complete, and comparison has been made to V583, the differences determined will be validated using microarrays produced by the oligonucleotide synthesis technology developed at NimbleGen. In addition to these novel methods, standard procedures will be use for shotgun sequencing, finishing, and validation of genomic sequence differences. The introduction of the novel methods will reduce costs and increase throughput, both of which are important for future scale-up to larger numbers of strains.

描述（申请人提供）：粪肠球菌是一种重要的医院病原菌。虽然粪肠杆菌是正常人类肠道菌群的组成部分，但它是一种低毒力的生物。然而，由粪肠球菌引起的各种感染也会发生，包括心内膜炎、菌血症、泌尿道和其他组织感染。引起这些感染的粪肠杆菌菌株在毒力因子上可能与居住在健康人肠道中的温顺菌株不同。因此，确定具有不同表型的粪肠球菌菌株之间的遗传差异是一个重要的挑战。