Oral Streptococcal Fitness And Virulence genes

口腔链球菌适应性和毒力基因

• 批准号: 10296913
• 负责人: TODD O. KITTEN
• 金额: $ 53.43万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-03 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10296913
• 关键词: Affect; Antibiotic Resistance; Antibiotics; Bacteria; Binding; Bioinformatics; Biological Assay; Blood; Blood Circulation; Blood Platelets; ChIP-seq; Dental; Dental Care; Dentists; Development; Disease; Endocarditis; Environment; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Genomics; Goals; Growth; Heart; Heart Valves; Human; Infection; Infective endocarditis; Libraries; Mastication; Methods; Microbial Biofilms; Modeling; Molecular; Mutation; Open Reading Frames; Oral; Oral cavity; Oral health; Oryctolagus cuniculus; Output; Pathogenesis; Pathway Analysis; Patients; Periodontal Diseases; Phagocytosis; Phenotype; Prevention strategy; RNA; Research; Saliva; Serum; Streptococcus; Streptococcus sanguis; Systems Biology; Technology; Tooth structure; Toothbrushing; Transcriptional Regulation; Virulence; Virulence Factors; Western Blotting; base; commensal bacteria; fitness; gene function; genome-wide; in vivo; indexing; member; mortality; mutant; new therapeutic target; novel strategies; novel vaccines; nutrition; oral bacteria; oral commensal; oral lesion; oral streptococci; prevent; prophylactic; protein expression; screening; transcription factor; transcriptome sequencing

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.

项目摘要 血链球菌是一种口腔细菌，是一种先锋定植菌 人类的牙齿它与感染性心内膜炎有关，可以进入 血液通过口腔病变，侵入性牙科手术或常规口腔 咀嚼、使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适应性创造了机会 基因作为一个整体的系统生物学本申请在目标1中提出， S.感染性心内膜炎模型中的sanguinis适应性 筛选一个独特的、全面的S.血吸虫全基因组突变体。 在目标2中，将使用以下方法在唾液、血清和血液中进行可比分析： ORF-seq分析，以澄清Aim 1的发现并鉴定Aim 1所需的基因。 健康，但不是唾液的增长。唾液和血液中的健康基因 比较了位于关键枢纽的适应性基因将在 网络分析和那些在口腔链球菌中保守的将被 通过生物信息学鉴定。在目标3中，适应基因的基因调节将是 深入研究。这一系统分析将提供前所未有的 在分子水平上了解链球菌适应性基因， 识别新治疗剂或预防剂的特定靶点的阶段。