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从中国分离的 2 株猪链球菌比较基因组学看链球菌中毒性休克综合征

A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates.

机构信息

Beijing Genomics Institute, Chinese Academy of Sciences, Beijing, China.

出版信息

PLoS One. 2007 Mar 21;2(3):e315. doi: 10.1371/journal.pone.0000315.

Abstract

BACKGROUND

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood.

METHODS AND FINDINGS

To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence.

CONCLUSIONS

To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.

摘要

背景

猪链球菌 2 型(SS2)是一种重要的人畜共患病病原体,在全球范围内已导致 200 多例严重人类感染,其特征为脑膜炎、败血症、关节炎等。最近,SS2 被认为是链球菌中毒性休克综合征(STSS)的病原体,而 STSS 最初与链球菌属中的化脓性链球菌(GAS)有关。然而,STSS 的分子机制仍知之甚少。

方法和发现

为阐明 SS2 引起 STSS 的遗传决定因素,对 3 株不同的中国 SS2 菌株进行了全基因组测序。通过比较基因组学和一系列实验,包括动物感染实验、PCR 检测和表达分析,进一步剖析了一个候选致病性岛(PAI)。本研究首次深入了解了导致中国两起大规模人类 STSS 暴发的高度侵袭性中国 SS2 分离株的新型分子机制。我们在基因组水平上研究了一个约 89kb 长的候选 PAI,将其命名为 89K,该 PAI 特异性存在于中国 SS2 毒力分离株中。它具有 PAI 的普遍特征,如独特的 GC 含量,这与其在 STSS 中的关键作用和高毒力一致。

结论

据我们所知,这是全球范围内首次从猪链球菌中发现的 PAI 候选物。我们的研究结果从基因组水平上阐明了 SS2 引发的 STSS,有助于进一步了解其发病机制,并为针对高度致病性 SS2 感染的有效策略的开发指明了方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/105f/1820848/01f06e92980a/pone.0000315.g001.jpg

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