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Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis

机译：W，ST-11脑膜炎奈瑟氏球菌高毒血清群的基因组流行病学

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Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally with dynamic strain distribution over time. Beginning with an epidemic among Hajj pilgrims in 2000, serogroup W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African 'meningitis belt' and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate sporadic W ST-11 strains in circulation since 1970 from the Hajj outbreak strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters are caused by direct descendants of the Hajj clone. Whole genome sequences of 270 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2013 were compared using whole genome phylogenetic and major antigen-encoding gene sequence analyses. We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. The Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone recombination involving virulence genes encoding factor H binding protein, nitric oxide reductase, and nitrite reductase. These data demonstrate that recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes was associated with the emergence of the Hajj clone. Importantly, W ST-11 strains unrelated to the Hajj outbreak contribute a significant proportion of W ST-11 cases globally. This study helps illuminate genomic factors associated with meningococcal strain emergence and evolution.
机译：脑膜炎奈瑟氏球菌是全球败血症和脑膜炎的主要细菌原因，随着时间的流逝动态分布。从2000年朝Ha朝圣者开始流行，血清型W（W）序列类型（ST）11成为非洲“脑膜炎带”流行性脑膜炎的主要原因，并在南美，欧洲，中东和中国流行。自1970年以来，以前的基因分型研究无法可靠地将散发的W ST-11菌株与朝j暴发株（朝aj克隆）区分开。同样不清楚的是，最近朝圣的W ST-11疾病群中有多大比例是由朝j克隆的直接后代引起的。使用全基因组系统发育和主要抗原编码基因序列分析，比较了1970年至2013年从全球侵袭性脑膜炎球菌病患者中分离的270株脑膜炎球菌菌株的全基因组序列。我们发现所有W ST-11菌株是祖先菌株的后代，该祖先菌株经历了独特的荚膜转换事件。 Hajj克隆及其后代与其他W ST-11菌株不同，因为它们具有共同的抗原基因图谱，并已进行了重组，涉及编码因子H结合蛋白，一氧化氮还原酶和亚硝酸还原酶的毒力基因。这些数据表明，最近获得的独特的抗原编码基因谱和脑膜炎球菌毒力基因的变异与朝j克隆的出现有关。重要的是，与朝j爆发无关的W ST-11毒株占全球W ST-11病例的很大比例。这项研究有助于阐明与脑膜炎球菌菌株出现和进化有关的基因组因素。

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