Pilin Genotyping for Group A Streptococci

项目总结 A组链球菌(GAS)是一种全球重要的人类病原体，主要感染喉咙 (咽炎)或皮肤(脓疱病)，每年导致约7.5亿人感染；发病率和死亡率高 是由侵袭性疾病和自身免疫性并发症引起的。尽管它作为一种全球病原体很重要，但在那里 目前还没有预防瓦斯病的疫苗可用。 全球天然气种群高度多样化，在很大程度上是由于抗原性的高度异质性。 在细胞表面蛋白中。多样性是通过广泛的水平基因转移扩大的，这是 这个物种产生了许多独特的表面蛋白抗原组合。然而，一种与生物相关的 毒气“菌株”的标准定义还很欠缺。从历史上看，两种血清学分型方案(M和T)是 用于表征GAS菌株：M分型是基于短M蛋白表面原纤维，T分型是基于 在细长的菌毛上。除了高度的序列多样性外，M蛋白和菌毛也是关键的毒力因子 是宿主保护性免疫的目标。M分型已被emm基因分型所取代。建议数 该项目寻求开发一种基于序列的GAS菌毛(即T抗原)的分型方案。 该研究的具体目标是开发一种基于粘附素和主干菌毛蛋白基因的菌毛蛋白基因分型方案。 来自全球不同的GAS分离株的基因组序列是最初 菌毛基因数据库；序列将进行系统发育分析并分配到簇中。数据将是 策划并在一个方便用户的网站www.pubmlst.org上公开提供。Pilin类型将被组合 带有EMM类型和MLST定义的序列类型，以产生气体“菌株”的定义。 拟议的工作将为这一全球主要疾病提供改进的分子流行病学分型方案 病原体。术语的标准化可以促进气田中的“应变”比较，并使 快速识别新出现的菌株。Pilin打字还将为未来的工作提供基础，从而导致 解决不同类型气体疾病发病的分子基础的新假说，以及 新菌株出现和免疫逃逸的遗传基础。丰富的分子流行病学数据可以 还促进采取合理的疫苗设计方法和疫苗接种战略。阐明问题的进展 致病的分子机制和研制GAS疫苗是长期的目标。

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.