Oral Streptococcal Fitness And Virulence genes

项目摘要 血链球菌是一种共生性口腔细菌，也是一种先驱定殖者。 人类牙齿的。它与感染性心内膜炎有关，并可进入 通过口腔损伤、侵入性牙科手术或常规口腔进行血流 咀嚼、用牙线和刷牙等活动。最近的事态发展 基因组技术为研究链球菌的适合性创造了机会 系统生物学将基因作为一个整体来研究。此应用程序在目标1中建议识别 感染性心内膜炎模型中血链球菌适合性所需基因 筛选一个独特的、全面的血链球菌全基因组突变文库。 在目标2中，将对唾液、血清和血液进行可比性分析 ORF-SEQ分析，以澄清AIM 1的发现并确定 健康，但不是唾液的增长。唾液和血液中的健康基因将是 比较一下。位于关键枢纽的健身基因将在 网络分析和在口腔链球菌中保守的那些将是 由生物信息学鉴定。在目标3中，健身基因的基因调节将是 深入研究。这一系统的分析将提供前所未有的 从分子水平了解链球菌的适合性基因并设置 确定新疗法或预防药物的特定靶点的阶段。

Project Summary Streptococcus sanguinis is a commensal oral bacterium and a pioneer colonizer of human teeth. It is associated with infective endocarditis and can enter the bloodstream through oral lesions, invasive dental procedures or routine oral activities such as chewing, flossing and brushing teeth. Recent developments in genomic technologies have created an opportunity to study streptococcal fitness genes as a whole by systems biology. This application proposes in Aim 1 to identify genes required for S. sanguinis fitness in an infective endocarditis model by screening a unique, comprehensive library of S. sanguinis genome-wide mutants. In Aim 2, a comparable analysis will be performed in saliva, serum and blood using ORF-seq analysis to clarify the findings of Aim 1 and to identify genes required for fitness, but not growth in saliva. The fitness genes in saliva and blood will be compared. Fitness genes that are located at critical hubs will be identified in network analysis and those that are conserved among oral streptococci will be identified by bioinformatics. In aim 3, the gene regulation of fitness genes will be studied in depth. This systematic analysis will provide an unprecedented understanding of streptococcal fitness genes at the molecular level and set the stage for identification of specific targets for new therapeutics or prophylactics.