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B 群链球菌 CC17 超强毒力克隆的荚膜转换:多糖疫苗开发的未来挑战。

Capsular switching in group B Streptococcus CC17 hypervirulent clone: a future challenge for polysaccharide vaccine development.

机构信息

Institut Cochin, Université Sorbonne Paris Descartes, Paris, France.

出版信息

J Infect Dis. 2012 Dec 1;206(11):1745-52. doi: 10.1093/infdis/jis605. Epub 2012 Sep 21.

Abstract

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.

摘要

背景

荚膜多糖(CPS)是主要新生儿病原体 B 群链球菌(GBS)的重要毒力因子和疫苗靶标。群体研究表明,CPS 型与多位点序列分型(MLST)群之间没有很强的相关性,除了具有全球传播性的高毒力 GBS CC17 外,这一现象非常显著,而 CC17 菌株此前均为 CPS 型 III。

方法

对法国分离的 965 株侵袭性感染的 GBS 菌株进行 CPS 分型,并研究 CC17 特异性表面蛋白编码基因 hvgA 基因的存在情况。从筛选出的 3 株 hvgA 阳性 GBS 菌株中发现 CPS 型 IV 令人惊讶,因此进一步进行 MLST 分型、脉冲场凝胶电泳(PFGE)和全基因组测序进行特征分析。

结果

MLST 和 PFGE 表明,在高度同质的 GBS CC17 中,荚膜从 CPS 型 III 转变为 IV。序列分析表明,这种荚膜转换是由于含有整个 cps 操纵子的 35.5kb DNA 片段的交换。

结论

本研究表明,GBS CC17 高毒力菌株已切换了其主要疫苗靶标之一。因此,在结合 GBS 疫苗的临床试验期间,对 GBS 群体的持续监测仍然至关重要。

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