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首页> 外文期刊>EBioMedicine >Will Genome Analysis Elucidate Evolution, Global Transmission and Virulence of Neisseria Meningitidis Lineages?
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Will Genome Analysis Elucidate Evolution, Global Transmission and Virulence of Neisseria Meningitidis Lineages?

机译：基因组分析会阐明脑膜炎奈瑟氏球菌谱系的进化，整体传播和毒力吗？

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Neisseria meningitidis is a frequent commensal resident of theoropharyngealmucosa, carried by at least 10% of the human populationin industrialized countries. However, N. meningitidis might penetratethe mucosal membranes and cause life-threatening septicemia andmeningitis, commonly with a short time from onset to death. Despiteappropriate treatment, the case-fatality rate for invasive meningococcaldisease (IMD) remains around 10% (Goldacre et al., 2003). The bacteriumusesdifferent strategies to evade the immune systemand survive indifferent environments, nevertheless, the only truly well-establishedvirulence factor is the polysaccharide capsule. Thirteen serogroups differentiatedbased on the polysaccharide capsule have been identified,but only six of them(A, B, C,W, X and Y) account formost IMD globally.To control IMD, glycoconjugate vaccines have been developed targetingserogroups A, C, W, and Y (Cohn and Harrison, 2013). It is essentialwitha universal vaccine also for meningococcal serogroup B (MenB),the predominant etiology of IMD in many countries, which has notbeen successful due to the poor immunogenicity of the MenB capsulepolysaccharide. Therefore, the development of a universal MenB vaccinehas focused on conserved protein antigens (Giuliani et al., 2006)and, recent decade, reverse vaccinology (genome-based vaccine discovery)that has resulted in the 4 component meningococcus group B(4CMenB) vaccine (Bexsero; Novartis, MA, US) (O'Ryan et al., 2014).However, due to the selective pressure of 4CMenB new MenB antigenicvariants may emerge and reduce the vaccine efficacy. Consequently,careful monitoring of the MenB strain population with high-resolutiontyping methods is crucial. The genetic diversity and population structureofN.meningitidis have historically been characterized bymultilocusenzyme electrophoresis (MLEE) and subsequently multilocus sequencetyping (MLST) based on seven slowly-evolving housekeeping genes(Maiden et al., 1998). In general, relatively few meningococcal genotypes,clonal complexes or evolutionary lineages have caused most ofthe IMDworldwide, and these virulentmeningococcal variants diversifyas they spread in human populations. As an example, since the 1970smany MenB outbreaks have been caused by strains belonging to thehyperinvasive lineage ST-32 initially described in Norway in 1969 andlater described in many other countries worldwide (Caugant et al.,1987). Using whole genome sequencing (WGS), it is for the first timepossible to elucidate many issues regarding pathogen outbreaks andpandemicswith a high throughput, short turnaround time (using effectiveanalysis pipeline) and ideal resolution, which might provide informationeven about individual transmission events.
机译：脑膜炎奈瑟氏球菌是口咽粘膜的常见常住居民，在工业化国家中至少有10％的人口被携带。然而，脑膜炎奈瑟氏球菌可能会穿透粘膜并引起危及生命的败血病和脑膜炎，通常从发病到死亡的时间很短。尽管进行了适当的治疗，但侵袭性脑膜炎双球菌病（IMD）的致死率仍保持在10％左右（Goldacre等，2003）。细菌使用不同的策略来逃避免疫系统并在不同的环境中生存，但是，唯一真正确定的毒力因子是多糖胶囊。已鉴定出基于多糖荚膜分化的13个血清群，但其中只有6个（A，B，C，W，X和Y）占全球IMD的最大比例。为了控制IMD，已针对A，C，W血清群开发了糖结合疫苗。和Y（Cohn and Harrison，2013）。它对于B型脑膜炎球菌血清群（MenB）也是通用疫苗，这在许多国家都是IMD的主要病因，但由于MenB胶囊多糖的免疫原性较差，因此尚未成功。因此，通用的MenB疫苗的开发侧重于保守的蛋白抗原（Giuliani等，2006），近十年来，反向疫苗学（基于基因组的疫苗发现）导致了4组分B型脑膜炎球菌疫苗（4CMenB） （Bexsero;美国马萨诸塞州诺华市）（O'Ryan et al。，2014），但是由于4CMenB的选择性压力，可能会出现新的MenB抗原变体并降低疫苗效力。因此，使用高分辨率分型方法仔细监测MenB菌株种群至关重要。脑膜炎奈瑟氏球菌的遗传多样性和种群结构在历史上已经通过多位酶电泳（MLEE）和随后基于七个缓慢进化的管家基因的多位点测序（MLST）进行了表征（Maiden等，1998）。通常，世界范围内的大多数IMD引起的脑膜炎球菌基因型，克隆复合体或进化谱系相对较少，并且这些致病性脑膜炎球菌变异体随着在人群中的传播而多样化。例如，自1970年代以来，MenB暴发是由属于高侵袭性谱系ST-32的菌株引起的，该菌株最初于1969年在挪威描述，后来在世界许多其他国家描述（Caugant等，1987）。使用全基因组测序（WGS），首次有可能阐明关于病原体暴发和大流行的许多问题，这些问题具有高通量，较短的周转时间（使用有效分析流水线）和理想的分辨率，甚至可以提供有关单个传播事件的信息。

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