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.

项目摘要 A组链球菌（气）是一种全球重要性的人类病原体，主要感染喉咙 （咽炎）或皮肤（盗窃），每年大约7.5亿感染；发病率和死亡率高 是由于侵入性疾病和自身免疫并发症。尽管它是全球病原体的重要性，但 不能用于预防气体疾病的疫苗。 全球天然气人口高度潜水员，在很大程度上是由于高度抗原异质性 在细胞表面蛋白中。通过广泛的水平基因转移来扩大多样性 该物种产生了表面蛋白抗原的多种独特组合。但是，与生物学相关的 缺乏对气体“应变”的标准化定义。从历史上看，两个血清学打字方案（M和T）是 用于表征气体应变的：M型基于短M蛋白表面原纤维，T型基于 在细长的菌毛上。除了高序列多样性之外，M蛋白和Pili充当关键病毒因素 并且是宿主受保护的免疫力的靶标。 EMM基因分型已经取代了M型。提议 项目旨在为气体pili（即T-抗原）开发基于序列的打字方案。 特定目的旨在开发基于粘附素和骨干pilin基因的PILIN基因分型方案。 来自全球且多样化的气体分离株收集的基因组序列是初始材料的原始材料 PILIN基因的数据库；序列将进行系统发育分析并向簇分配。数据将是 在www.pubmlst.org上策划并公开提供，这是一个用户友好的网站。 PILIN类型将合并 具有EMM类型和MLST定义的序列类型，以产生气体“应变”的定义。 拟议的工作将为这一主要全球提供改进的分子流行病学分型方案 病原。命名法的标准化可以促进气场中的“应变”比较并启用 快速认识新出现的菌株。 PILIN打字还将为未来的工作提供基础 针对不同类型气疾病的发病机理的分子基础的新假设， 新的应变出现和免疫发现的遗传基础。丰富的分子流行病学数据可以 还促进了疫苗设计和疫苗策略的理性方法。迈向阐明的进展 发病机理和开发气体疫苗的分子机制是长期目标。