Biofilms and Enterococcus faecalis Biology

生物膜和粪肠球菌生物学

• 批准号: 7226681
• 负责人: GARY M DUNNY
• 金额: $ 35.44万
• 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/7226681
• 关键词: Animal Model; Antibiotic Resistance; Antimicrobial Resistance; Biology; Catheters; Coupled; Cryopreservation; Disease; Disruption; Endocarditis; Enterococcus; Enterococcus faecalis; Environment; Genes; Genetic; Genetic Determinism; Genetic Materials; Genetic Screening; Genetic Transcription; Genomics; Growth; Heart Valves; Horizontal Gene Transfer; Hospitals; Human; Implant; In Vitro; Infection; Intestines; Lead; Life Style; Medical; Medical Device; Microbial Biofilms; Modeling; Molecular Genetics; Molecular Structure; Monitor; Opportunistic Infections; Organism; Oryctolagus cuniculus; Pathogenesis; Patients; Physiological; Physiology; Proteins; Reporter Genes; Reporting; Resistance; Resolution; Scanning Electron Microscopy; Staphylococcus aureus; Surface; System; Systemic infection; Technology; Testing; Vancomycin Resistance; Virulence; Work; antimicrobial drug; base; chemotherapeutic agent; implantable device; interest; mutant; novel; pathogen; pressure; research study; tube feeding

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，在健康人体内通常不具有致病性。然而，它已成为一个主要的院内病原体在受损患者，它可以引起高度致命形式的心内膜炎。肠球菌对抗菌素具有高度的固有耐药性，并倾向于通过水平转移获得和捐赠新的耐药基因，这增强了肠球菌的医学重要性。肠球菌通常从植入的医疗器械（如导管和喂食管）上形成的生物膜中分离出来，在心脏瓣膜上定植和生长可能代表了生物膜生长状态的一种形式。最近的一份报告表明，生物膜环境可能是肠球菌向金黄色葡萄球菌转移高水平万古霉素耐药性的利基。在本项目中，将使用体外和动物模型分析粪肠球菌生物膜形成的生理学和遗传学。这项工作可能会导致鉴定新的基因产物所需的有机体从共生生活方式到病原体的适应。该项目的具体目标是：