Characterisation of Neisseria meningitidis cc11/ET-15 variant by whole genome sequencing

BACKGROUND Neisseria meningitidis strains belonging to clonal complex 11 is the cause of numerous outbreaks and epidemics in the United States, Canada and Europe, accounting for 49.5% of cases of meningococcal disease caused by serogroup C worldwide. In Brazil, it is the second most frequent clonal complex within this serogroup. The genetic characterisation of cc11/ET-15 variants is important for the epidemiological monitoring of meningococcal disease, through the identification of circulating epidemic clones, to support specific actions of Health Surveillance aiming outbreaks control. OBJECTIVES The objective of this study was to identify features in the genome of cc11/ET-15 clones through whole-genome sequencing (WGS), that differ from cc11/non-ET-15 strains that could explain their virulence. METHODS The whole genome of three cc11/ET-15 representative strains were sequenced with a minimum coverage of 100X with the MiSeq System and compared to the genome of cc11/non-ET-15 strains. RESULTS Genome analysis of cc11/ET-15 variants showed the presence of resistance factors, mobile genetic elements and virulence factors not found in cc11/non-ET-15 strains. MAIN CONCLUSIONS Our results show that these strains carry virulence factors not identified in cc11/non-ET-15 strains, which could explain the high lethality rates attributed to this clone worldwide.

背景 隶属于克隆复合体11（clonal complex 11, CC11）的脑膜炎奈瑟菌（Neisseria meningitidis）菌株是美国、加拿大及欧洲多起暴发与流行事件的致病元凶，其所引发的病例占全球C群血清型脑膜炎球菌病总病例的49.5%。在巴西，该克隆复合体是此血清型中第二常见的致病克隆。通过识别流行致病克隆开展脑膜炎球菌病的流行病学监测，并为卫生监测部门制定暴发防控专项措施提供支撑，对CC11/ET-15变异株的遗传特性鉴定具有重要意义。
研究目标 本研究旨在通过全基因组测序（whole-genome sequencing, WGS）分析CC11/ET-15克隆的基因组特征，筛选出与CC11/非ET-15菌株存在差异的基因位点，以阐明前者的致病力机制。
研究方法 选取3株CC11/ET-15代表性菌株进行全基因组测序，测序最小覆盖度不低于100X，采用MiSeq测序系统完成测序，并将所得基因组序列与CC11/非ET-15菌株的基因组进行比对分析。
结果 CC11/ET-15变异株的基因组分析结果显示，其携带有CC11/非ET-15菌株未检出的耐药因子、可移动遗传元件与致病力因子。
主要结论 本研究结果表明，此类菌株携带CC11/非ET-15菌株未鉴定出的致病力因子，这或可解释该克隆在全球范围内引发的高致死率。