Streptococcal genomics and pathogenesis

链球菌基因组学和发病机制

• 批准号: 6605214
• 负责人: TODD O. KITTEN
• 金额: $ 9万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6605214
• 关键词: Streptococcus sanguis; bacteria infection mechanism; bacterial endocarditis; bacterial genetics; biotechnology; clinical research; functional /structural genomics; genetic manipulation; genetic mapping; genome; host organism interaction; human data; informatics; laboratory rabbit; laboratory rat; patient oriented research; postdoctoral investigator; septicemia; site directed mutagenesis; transposon /insertion element; virulence

DESCRIPTION (provided by applicant): Viridans streptococci are the leading cause of infective endocarditis, a serious illness which affects about 22,000 people per year in the US and kills over 2,000. These bacteria are also common agents of bacteremia, especially in neutropenic patients. Identification of streptococcal virulence factors would lead to a better understanding of the pathogenesis of streptococcal bacteremia and endocarditis and to the identification of targets for prevention and therapy. Dr. Todd Kitten is currently applying signature-tagged mutagenesis to identify Streptococcus sanguis virulence factors for endocarditis. This approach requires no prior assumptions concerning the importance of any particular gene or activity in disease causation. Instead, it relies on the infection process in an animal model to identify the bacterial genes needed for disease and their relative contributions. The proposed career development project will extend this work by providing Dr. Kitten with the bioinformatic skills necessary to perform sophisticated analyses of genes and pathways identified by signature tagging as required for virulence. The imminent completion at Virginia Commonwealth University of new, dedicated bioinformatic facilities, bioinformatic curricula, and the S. sanguis genome sequence have combined to create the perfect opportunity for Dr. Kitten to obtain and hone these skills. Of equal importance, Dr. Kitten will dramatically extend his expertise, perspective, and research material by engaging in infectious disease training activities and by obtaining clinical data and strains from patients infected with viridans streptococci. These activities will leverage the world-class teaching hospital and clinical researchers available at VCU. The clinical experience, data and strains will ensure that Dr. Kitten's research remains directed toward pressing and pragmatic clinical pursuits, while the bioinformatic training will ensure that he has the skills necessary to apply the latest and most suitable approaches to these pursuits.

描述（由申请人提供）：翠绿链球菌是感染性心内膜炎的主要原因，这是一种严重的疾病，在美国每年影响约22,000人，死亡人数超过2,000人。这些细菌也是引起菌血症的常见病原体，尤其是在中性粒细胞减少症患者中。确定链球菌毒力因子有助于更好地了解链球菌菌血症和心内膜炎的发病机制，并确定预防和治疗的靶点。Todd Kitten博士目前正在应用签名标记诱变技术来鉴定血链球菌心内膜炎的毒力因子。这种方法不需要预先假设任何特定基因或活动在致病中的重要性。相反，它依赖于动物模型中的感染过程来识别疾病所需的细菌基因及其相对贡献。拟议的职业发展项目将通过为Kitten博士提供必要的生物信息学技能来扩展这项工作，以执行通过签名标记识别的基因和途径的复杂分析。弗吉尼亚联邦大学即将完成的新的、专门的生物信息学设施、生物信息学课程和血链球菌基因组序列，为基滕博士获得和磨练这些技能创造了完美的机会。同样重要的是，Kitten博士将通过参与传染病培训活动和从感染翠绿链球菌的患者那里获得临床数据和菌株，极大地扩展他的专业知识、观点和研究材料。这些活动将充分利用VCU世界一流的教学医院和临床研究人员。临床经验、数据和菌株将确保基滕博士的研究仍然面向紧迫和实用的临床追求，而生物信息学培训将确保他具备将最新和最合适的方法应用于这些追求的必要技能。