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，通常对健康人无致病性。然而，它已成为一个主要的医院病原体在妥协的病人，它可以导致一个高度致命的形式心内膜炎。肠球菌的医学重要性因其对抗菌剂的高度固有抗性以及其通过水平转移获得和捐赠新抗性基因的倾向而增强。肠球菌通常从植入的医疗器械（如导管和饲管）上形成的生物膜中分离，并且在心脏瓣膜上的定植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，生物膜环境作为一个可能的利基转移高水平的万古霉素耐药性从肠球菌到金黄色葡萄球菌。本项目主要研究了大肠杆菌生物膜形成的生理学和遗传学机制。将使用体外和动物模型分析粪便。这项工作可能会导致识别新的基因产物所需的适应生物体从一个寄生虫的生活方式的病原体。该项目的具体目标是： 1)鉴定E.生物膜形成所需的粪菌遗传决定因素。 2)利用报告基因构建体来监测生物膜中的表达，并表征E。粪肠球菌适应生物膜的生长从浮游生长。 3)分析大肠杆菌的细胞和分子结构。粪便生物膜的高分辨率扫描电子显微镜。 4)检测所选生物膜缺陷突变体在实验性心内膜炎中的毒力。