PDF(Pubmed)
Abstract：
Among genes present in all group A streptococci (GAS), those encoding M-fibril and T-pilus proteins display the highest levels of sequence diversity, giving rise to the two primary serological typing schemes historically used to define strain. A new genotyping scheme for the pilin adhesin and backbone genes is developed and, when combined with emm typing, provides an account of the global GAS strain population. Cluster analysis based on nucleotide sequence similarity assigns most T-serotypes to discrete pilin backbone sequence clusters, yet the established T-types correspond to only half the clusters. The major pilin adhesin and backbone sequence clusters yield 98 unique combinations, defined as \"pilin types.\" Numerous horizontal transfer events that involve pilin or emm genes generate extensive antigenic and functional diversity on the bacterial cell surface and lead to the emergence of new strains. Inferred pilin genotypes applied to a meta-analysis of global population-based collections of pharyngitis and impetigo isolates reveal highly significant associations between pilin genotypes and GAS infection at distinct ecological niches, consistent with a role for pilin gene products in adaptive evolution. Integration of emm and pilin typing into open-access online tools (pubmlst.org) ensures broad utility for end-users wanting to determine the architecture of M-fibril and T-pilus genes from genome assemblies.IMPORTANCEPrecision in defining the variant forms of infectious agents is critical to understanding their population biology and the epidemiology of associated diseases. Group A Streptococcus (GAS) is a global pathogen that causes a wide range of diseases and displays a highly diverse cell surface due to the antigenic heterogeneity of M-fibril and T-pilus proteins which also act as virulence factors of varied functions. emm genotyping is well-established and highly utilized, but there is no counterpart for pilin genes. A global GAS collection provides the basis for a comprehensive pilin typing scheme, and online tools for determining emm and pilin genotypes are developed. Application of these tools reveals the expansion of structural-functional diversity among GAS via horizontal gene transfer, as evidenced by unique combinations of surface protein genes. Pilin and emm genotype correlations with superficial throat vs skin infection provide new insights on the molecular determinants underlying key ecological and epidemiological trends.
摘要：
在所有A组链球菌（GAS）中存在的基因中，编码M-原纤维和T-菌毛蛋白的序列多样性最高，产生了历史上用于定义菌株的两种主要血清学分型方案。开发了一种新的菌毛蛋白粘附素和骨架基因的基因分型方案，当结合emm打字时，提供了全球GAS菌株种群的说明。基于核苷酸序列相似性的聚类分析将大多数T血清型分配给离散的菌毛蛋白主链序列簇，然而，建立的T型只对应于一半的簇。主要的菌毛粘附素和骨架序列簇产生98个独特的组合，定义为\"pilin类型。“许多涉及pilin或emm基因的水平转移事件在细菌细胞表面产生广泛的抗原和功能多样性，并导致新菌株的出现。推断的pilin基因型应用于全球人群收集的咽炎和脓疱病分离株的荟萃分析，揭示了不同生态位的pilin基因型与GAS感染之间的高度显着关联。与菌毛蛋白基因产物在适应性进化中的作用一致。将emm和pilin分型整合到开放式在线工具（pubmlst.org）中，可确保最终用户希望从基因组组装中确定M-原纤维和T-菌毛基因的结构。IMPORTANCEPrecision定义感染因子的变体形式对于了解其种群生物学和相关疾病的流行病学至关重要。A组链球菌（GAS）是一种全球性病原体，由于M-原纤维和T-菌毛蛋白的抗原异质性，它还可以作为各种功能的毒力因子，因此会导致多种疾病并显示出高度多样化的细胞表面。EMM基因分型是建立和高度利用，但是Pilin基因没有对应的基因.全球GAS集合为全面的比林分型方案提供了基础，并开发了确定emm和pilin基因型的在线工具。这些工具的应用揭示了通过水平基因转移扩大GAS之间的结构功能多样性，表面蛋白基因的独特组合证明了这一点。Pilin和emm基因型与浅表咽喉和皮肤感染的相关性为关键生态和流行病学趋势的分子决定因素提供了新的见解。
