Pilin Genotyping for Group A Streptococci

A 组链球菌的 Pilin 基因分型

• 批准号: 10171765
• 负责人: Debra E BESSEN
• 金额: $ 7.8万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10171765
• 关键词: Abbreviations; Acute; Acute Glomerulonephritis; Address; Adopted; Antigen-Antibody Complex; Antigens; Autoimmune; Autoimmune Diseases; Bacteria; Bacterial Adhesins; Base Sequence; Binding; Biological; Biology; Cell Surface Proteins; Collection; Complex; Coupled; Data; Databases; Development; Disease; Disease Outbreaks; Distant; Epidemiological trend; Epidemiology; Epithelial; Fimbriae Proteins; Formulation; Foundations; Future; Genes; Genetic; Genome; Genomic DNA; Genotype; Geography; Goals; Heterogeneity; Horizontal Gene Transfer; Housekeeping; Human; Immune; Immunity; Impetigo; Individual; Infection; Infectious Agent; Knowledge; Language; Mediating; Membrane Proteins; Methods; Molecular; Molecular Epidemiology; Morbidity - disease rate; Nomenclature; Organism; Pathogenesis; Pathology; Pharyngeal structure; Pharyngitis; Phenotype; Phylogenetic Analysis; Phylogeny; Pilum; Population; Prevention; Process; Property; Public Health; Research Personnel; Resolution; Rheumatic Fever; Risk Factors; Scheme; Seasons; Serology; Serum Proteins; Skin; Skin Tissue; Soft Tissue Infections; Source; Standardization; Streptococcal Infections; Streptococcal Vaccines; Streptococcus pyogenes; Symptoms; Thinness; Time; Toxic Shock Syndrome; Vaccine Design; Vaccines; Variant; Vertebral column; Virulence Factors; Work; base; cost effective; epidemiologic data; human pathogen; improved; migration; mortality; multiple myeloma M Protein; next generation; next generation sequence data; next generation sequencing; pathogen; user-friendly; vaccination strategy; vaccine access; web site

PROJECT SUMMARY Group A Streptococcus (GAS) is a human pathogen of global importance that primarily infects the throat (pharyngitis) or skin (impetigo), leading to ~750 million infections per year; high rates of morbidity and mortality are due to invasive disease and autoimmune complications. Despite its importance as a global pathogen, there is no vaccine available for the prevention of GAS disease. The global GAS population is highly diverse, due in large part to the high degree of antigenic heterogeneity among cell surface proteins. Diversity is amplified via the extensive horizontal gene transfer that characterizes this species to yield numerous unique combinations of surface protein antigens. Yet, a biologically relevant and standardized definition for GAS “strain” is lacking. Historically, two serological typing schemes (M and T) were used to characterize GAS strains: M-typing is based on the short M protein surface fibril, and T-typing is based on thin elongated pili. In addition to high sequence diversity, the M protein and pili act as key virulence factors and are targets of host protective immunity. M-typing has been supplanted by emm genotyping. The proposed project seeks to develop a sequence-based typing scheme for GAS pili (i.e., T-antigens). The Specific Aim seeks to develop a pilin genotyping scheme based on adhesin and backbone pilin genes. Genome sequences from a global and diverse collection of GAS isolates are the source material for the initial database of pilin genes; sequences will undergo phylogenetic analysis and assignment to clusters. Data will be curated and made publicly available on www.pubmlst.org, a user-friendly website. Pilin type will be combined with emm type and MLST-defined sequence type to yield a definition for GAS “strain.” The proposed work will provide an improved molecular epidemiology typing scheme for this major global pathogen. Standardization of nomenclature can facilitate “strain” comparisons in the GAS field and enable rapid recognition of newly emerged strains. Pilin typing will also provide a foundation for future work leading to new hypotheses that address the molecular basis for pathogenesis of different types of GAS disease, and the genetic basis for new strain emergence and immune escape. The enriched molecular epidemiology data can also promote rational approaches to vaccine design and vaccination strategies. Progress towards elucidating the molecular mechanisms of pathogenesis and developing a GAS vaccine are long-term goals.

项目概要 A 组链球菌 (GAS) 是一种具有全球重要性的人类病原体，主要感染咽喉 （咽炎）或皮肤病（脓疱疮），每年导致约 7.5 亿人感染，发病率和死亡率很高； 尽管它作为一种全球病原体很重要，但它是由侵袭性疾病和自身免疫并发症引起的。 目前尚无疫苗可用于预防 GAS 疾病。 全球 GAS 群体高度多样化，很大程度上是由于高度的抗原异质性 细胞表面蛋白质之间的多样性通过广泛的水平基因转移而得到放大。 该物种产生许多独特的表面蛋白抗原组合，并且具有生物学相关性。 GAS“菌株”缺乏标准化定义 历史上，有两种血清学分型方案（M 和 T）。 用于表征 GAS 菌株：M 型分型基于短 M 蛋白表面原纤维，T 型分型基于 除了高序列多样性外，M 蛋白和菌毛也是关键的毒力因子。 和 是宿主保护性免疫的目标，已被 emm 基因分型所取代。 该项目旨在开发一种基于序列的 GAS pili（即 T 抗原）分型方案。 具体目标旨在开发基于粘附素和骨干菌毛蛋白基因的菌毛蛋白基因分型方案。 来自全球和多样化的 GAS 分离株的基因组序列是最初的材料 菌毛蛋白基因数据库；序列将进行系统发育分析并将数据分配给簇。 将在 www.pubmlst.org 上策划并公开，这是一个用户友好的 Pilin 类型网站。 使用 emm 类型和 MLST 定义的序列类型来生成 GAS“应变”的定义。 拟议的工作将为这一主要的全球流行病学分型方案提供改进的分子流行病学分型方案。 病原体命名法的标准化可以促进 GAS 领域的“菌株”比较，并使之成为可能。 对新出现的感染的快速识别也将为未来的工作奠定基础。 解决不同类型 GAS 疾病发病机制的分子基础的新假设，以及 丰富的分子流行病学数据可以为新毒株的出现和免疫逃逸提供遗传基础。 还促进疫苗设计和疫苗接种策略的合理方法。 发病机制的分子机制和开发 GAS 疫苗是长期目标。