Streptococcal genomics and pathogenesis

链球菌基因组学和发病机制

• 批准号: 6750123
• 负责人: TODD O. KITTEN
• 金额: $ 9.27万
• 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/6750123
• 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）：Viridans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，每年影响约22,000人，杀死了2000多人。这些细菌也是菌血症的常见药物，尤其是在中性粒细胞减少患者中。鉴定链球菌毒力因子将使人们更好地了解链球菌细菌和心内膜炎的发病机理，并确定预防和治疗靶标。托德小猫博士目前正在应用标志性的诱变，以鉴定心内膜炎的链球菌毒力因子链球菌。这种方法不需要以前关于任何特定基因或活性在疾病因果关系中的重要性的事先假设。取而代之的是，它依靠动物模型中的感染过程来识别疾病及其相对贡献所需的细菌基因。拟议的职业发展项目将通过为小猫博士提供生物信息学技能来扩展这项工作，以进行对基因和途径进行复杂分析所需的生物信息技能，并通过签名标记为毒力所需的签名标记确定。弗吉尼亚州新的，敬业的生物信息学设施，生物信息学课程和S. sanguis基因组序列即将完成，共同创造了基因博士获得和磨练这些技能的绝佳机会。同样重要的是，小猫博士将通过从事传染病训练活动，并从感染Viridans链球菌感染的患者中获得临床数据和菌株来大大扩展其专业知识，观点和研究材料。这些活动将利用VCU的世界一流教学医院和临床研究人员。临床经验，数据和压力将确保小猫博士的研究仍然针对紧迫和务实的临床追求，而生物信息学培训将确保他具有将最新和最合适的方法应用于这些追求的必要技能。