Capsular Switching in Group B Streptococcus CC17 Hypervirulent Clone: A Future Challenge for Polysaccharide Vaccine Development
Capsular Switching in Group B Streptococcus CC17 Hypervirulent Clone: A Future Challenge for Polysaccharide Vaccine Development
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DOI：
10.1093/infdis/jis605
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发表时间：
2012-12-01
影响因子：
6.4
通讯作者：
Poyart, Claire
中科院分区：
文献类型：
--
作者：
Bellais, Samuel;Six, Anne;Poyart, Claire
背景。荚膜多糖（CPS）是主要新生儿病原体B族链球菌（GBS）的重要毒力因子和疫苗靶标。人群研究表明，CPS 类型与多位点序列分型 (MLST) 簇之间没有很强的相关性，但高毒力 GBS CC17 在全球范围内传播是一个显着的例外，直到最近，这些疾病都属于 CPS III 型。方法。对法国分离的 965 株侵袭性感染 GBS 菌株进行了 CPS 分型，并研究了 CC17 特异性表面蛋白编码基因 hvgA 基因的存在。筛选出的三个 hvgA 阳性 GBS 菌株令人惊讶地为 CPS IV 型，因此通过 MLST 分型、脉冲场凝胶电泳 (PFGE) 和全基因组测序进一步表征。结果。 MLST 和 PFGE 证明了在高度同质的 GBS CC17 内从 CPS III 型到 IV 型的囊膜转换。序列分析表明，这种荚膜开关是由于包含整个 cps 操纵子的 35.5 kb DNA 片段的交换所致。结论。这项工作表明 GBS CC17 高毒株已经改变了其主要疫苗目标之一。因此，在 GBS 结合疫苗的临床试验期间，对 GBS 人群的持续监测仍然至关重要。
Background. The capsular polysaccharide (CPS) is an important virulence factor and a vaccine target of the major neonatal pathogen group B Streptococcus (GBS). Population studies revealed no strong correlation between CPS type and multilocus sequence typing (MLST) cluster, with the remarkable exception of the worldwide spread of hypervirulent GBS CC17, which were all until recently CPS type III.Methods. A total of 965 GBS strains from invasive infection isolated in France were CPS typed and the presence of the CC17-specific surface protein encoding gene hvgA gene was investigated. Three hvgA-positive GBS strains screened were surprisingly CPS type IV and thus further characterized by MLST typing, pulsed-field gel electrophoresis (PFGE), and whole genome sequencing.Results. MLST and PFGE demonstrated a capsular switching from CPS type III to IV within the highly homogeneous GBS CC17. Sequence analysis revealed that this capsular switch was due to the exchange of a 35.5-kb DNA fragment containing the entire cps operon.Conclusions. This work shows that GBS CC17 hypervirulent strains have switched one of their main vaccine targets. Thus, continued surveillance of GBS population remains of the utmost importance during clinical trials of conjugate GBS vaccines.