Oral Streptococcal Fitness And Virulence genes

口腔链球菌适应性和毒力基因

基本信息

批准号：
10461116
负责人：
TODD O. KITTEN
金额：
$ 52.9万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
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/10461116
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

项目摘要

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 Sanguinis链球菌是一种共同的口服细菌和先锋菌落剂人牙的牙齿。它与感染性心内膜炎有关，可以进入通过口腔病变，侵入性牙科手术或常规口服血液咀嚼，牙线和刷牙等活动。最近的发展基因组技术创造了一个研究链球菌健康的机会整个基因通过系统生物学。本申请在AIM 1中提议确定在感染性心内膜炎模型中，S. sanguinis适应性所需的基因筛选全基因组突变体的独特，全面的库。在AIM 2中，将在唾液，血清和血液中进行可比的分析 ORF-seq分析以阐明目标1的发现并确定所需的基因健身，但唾液中没有增长。唾液和血液中的健身基因将是比较的。位于关键枢纽的健身基因将在网络分析以及在口腔链球菌中保守的网络分析将是通过生物信息学识别。在AIM 3中，适应性基因的基因调节将是深入研究。这种系统分析将提供前所未有的了解分子水平的链球菌适应性基因，并设置鉴定新疗法或预防药物的特定靶标的阶段。