School of Biology, Georgia Institute of Technology, Atlanta, Georgia, USA.
J Bacteriol. 2012 Oct;194(20):5649-56. doi: 10.1128/JB.06604-11. Epub 2012 Aug 17.
Containment strategies for outbreaks of invasive Neisseria meningitidis disease are informed by serogroup assays that characterize the polysaccharide capsule. We sought to uncover the genomic basis of conflicting serogroup assay results for an isolate (M16917) from a patient with acute meningococcal disease. To this end, we characterized the complete genome sequence of the M16917 isolate and performed a variety of comparative sequence analyses against N. meningitidis reference genome sequences of known serogroups. Multilocus sequence typing and whole-genome sequence comparison revealed that M16917 is a member of the ST-11 sequence group, which is most often associated with serogroup C. However, sequence similarity comparisons and phylogenetic analysis showed that the serogroup diagnostic capsule polymerase gene (synD) of M16917 belongs to serogroup B. These results suggest that a capsule-switching event occurred based on homologous recombination at or around the capsule locus of M16917. Detailed analysis of this locus uncovered the locations of recombination breakpoints in the M16917 genome sequence, which led to the introduction of an ∼2-kb serogroup B sequence cassette into the serogroup C genomic background. Since there is no currently available vaccine for serogroup B strains of N. meningitidis, this kind capsule-switching event could have public health relevance as a vaccine escape mutant.
针对侵袭性奈瑟脑膜炎球菌疾病爆发的控制策略是通过对多糖荚膜进行血清型分析来确定的。我们试图揭示来自急性脑膜炎球菌病患者的分离株（M16917）血清型分析结果相互矛盾的基因组基础。为此，我们对 M16917 分离株的全基因组序列进行了特征描述，并针对已知血清型的脑膜炎奈瑟球菌参考基因组序列进行了多种比较序列分析。多位点序列分型和全基因组序列比较表明，M16917 是 ST-11 序列群的成员，该序列群通常与血清型 C 相关。然而，序列相似性比较和系统发育分析表明，M16917 的血清型诊断荚膜聚合酶基因（synD）属于血清型 B。这些结果表明，基于 M16917 荚膜基因座或其周围的同源重组发生了荚膜转换事件。对该基因座的详细分析揭示了 M16917 基因组序列中重组断点的位置，导致大约 2kb 的血清型 B 序列盒被引入到血清型 C 基因组背景中。由于目前尚无针对脑膜炎奈瑟球菌血清型 B 菌株的疫苗，这种荚膜转换事件可能成为疫苗逃逸突变体，具有公共卫生相关性。
