Biofilms and Enterococcus faecalis Biology

生物膜和粪肠球菌生物学

• 批准号: 6968394
• 负责人: GARY M DUNNY
• 金额: $ 31.77万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6968394
• 关键词: Enterococcus; bacterial genetics; biofilm; cryopreservation; endocarditis; gene expression; genetic screening; laboratory rabbit; microarray technology; mutant; nosocomial infections; quorum sensing; reporter genes; scanning electron microscopy; virulence

DESCRIPTION (provided by applicant): Enterococcus faecalis is a normal inhabitant of the mammalian intestinal tract, and is not normally pathogenic in healthy humans. However, it has become a major nosocomial pathogen in compromised patients and it can cause a highly fatal form of endocarditis. The medical importance of the enterococci is enhanced by their high degree of inherent resistance to antimicrobial agents, and their propensity to both acquire and to donate novel resistance genes by horizontal transfer. Enterococci are commonly isolated from biofilms formed on implanted medical devices such as catheters and feeding tubes, and colonization and growth on heart valves may represent a form of the biofilm growth state. A recent report suggests the biofilm environment as a likely niche for transfer of high-level vancomycin resistance from enterococci to Staphylococcus aureus. In this project, the physiology and genetics of biofilm formation in E. faecalis will be analyzed using both in vitro and animal models. This work could lead to the identification of novel gene products required for the adaptation of the organisms from a commensal lifestyle to that of a pathogen. The specific aims of the project are: 1) To identify the E. faecalis genetic determinants required for biofilm formation. 2) To use reporter gene constructs to monitor expression in biofilms, and to characterize the sensing machinery used by E. faecalis to adapt to biofilm growth from planktonic growth. 3) To analyze the cellular and molecular structure of E. faecalis biofilms using high resolution scanning electron microscopy. 4) To test the virulence of selected biofilm-deficient mutants in experimental endocarditis.

描述（由申请人提供）：粪肠球菌是哺乳动物肠道的正常居民，在健康的人类中通常并不是致病性的。但是，它已成为受损的患者的主要医院病原体，可能会导致高度致命的心内膜炎。肠球菌的医学重要性通过其对抗菌剂的固有耐药性以及它们通过水平转移而获得和捐赠新型抗药性基因的倾向来增强。肠球菌通常是从植入的医疗设备（例如导管和进食管）上形成的生物膜中分离出来的，心脏瓣膜上的定殖和生长可能代表生物膜生长状态的一种形式。最近的一份报告表明，生物膜环境可能是将高水平万古霉素耐药从肠球菌转移到金黄色葡萄球菌的转移。在这个项目中，将使用体外和动物模型分析粪肠球菌中生物膜形成的生理和遗传学。这项工作可能导致鉴定出从共生生活方式适应病原体所需的新型基因产物。该项目的具体目的是： 1）确定生物膜形成所需的粪肠球菌遗传决定因素。 2）使用报告基因构建体来监测生物膜中的表达，并表征大肠杆菌用来适应浮游生长的生物膜生长的传感机制。 3）使用高分辨率扫描电子显微镜分析粪肠球菌生物膜的细胞和分子结构。 4）测试在实验性心内膜炎中选定的缺乏生物膜突变体的毒力。