Identification of a novel virulence determinant with serum opacification activity in Streptococcus suis
Identification of a novel virulence determinant with serum opacification activity in Streptococcus suis
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DOI：
10.1128/iai.00359-06
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发表时间：
2006-11-01
影响因子：
3.1
通讯作者：
Valentin-Weigand, Peter
中科院分区：
文献类型：
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作者：
Baums, Christoph G.;Kaim, Ute;Valentin-Weigand, Peter
猪链球菌2型是一种猪和人的病原体，具有粘附性和侵袭性。在其他链球菌中，MSCRAMM家族(识别粘连基质分子的微生物表面成分)的大表面相关蛋白(>；100 kDa)是与宿主组织相互作用的关键角色。在这项研究中，我们鉴定了一种新的猪链球菌不透明因子(OFS)，其结构与MSCRAMM家族的成员具有同源性。OFS的N-末端与乳链球菌的纤维连接蛋白结合蛋白A(FnBA)和化脓性链球菌的血清不透明因子(SOF)同源。与这两种蛋白类似，OFS的N-末端结构域使马血清不透明。在野生型猪链球菌的十二烷基硫酸钠提取物中检测到血清混浊活性，而在同基因的Ofs基因敲除突变体的提取物中检测到血清混浊活性。OFS在乳酸乳球菌中的异源表达表明，OFS的高水平表达足以提供表面相关的血清混浊活性。此外，重组OFS抗血清可抑制血清混浊。OFS的C末端重复序列元件与FnBA和SOF的相应重复区域以及MSCRAMM的纤维连接蛋白结合重复序列的共同序列显著不同。因此，在重组的OFS中没有检测到纤维连接蛋白结合。为了探讨OFS基因在猪链球菌侵袭性疾病发病机制中的可能作用，将ofs基因通过框内缺失敲除的等基因突变株感染仔猪。突变株的毒力严重减弱，但在定殖过程中未见明显变化，表明OFS代表了猪链球菌的一种新的毒力决定因子。
Streptococcus suis serotype 2 is a porcine and human pathogen with adhesive and invasive properties. In other streptococci, large surface-associated proteins (> 100 kDa) of the MSCRAMM family (microbial surface components recognizing adhesive matrix molecules) are key players in interactions with host tissue. In this study, we identified a novel opacity factor of S. suis (OFS) with structural homology to members of the MSCRAMM family. The N-terminal region of OFS is homologous to the respective regions of fibronectin-binding protein A (FnBA) of Streptococcus dysgalactiae and the serum opacity factor (SOF) of Streptococcus pyogenes. Similar to these two proteins, the N-terminal domain of OFS opacified horse serum. Serum opacification activity was detectable in sodium dodecyl sulfate extracts of wild-type S. suis but not in extracts of isogenic ofs knockout mutants. Heterologous expression of OFS in Lactococcus lactis demonstrated that a high level of expression of OFS is sufficient to provide surface-associated serum opacification activity. Furthermore, serum opacification could be inhibited by an antiserum against recombinant OFS. The C-terminal repetitive sequence elements of OFS differed significantly from the respective repeat regions of FnBA and SOF as well as from the consensus sequence of the fibronectin-binding repeats of MSCRAMMs. Accordingly, fibronectin binding was not detectable in recombinant OFS. To investigate the putative function of OFS in the pathogenesis of invasive S. suis diseases, piglets were experimentally infected with an isogenic mutant strain in which the ofs gene had been knocked out by an in-frame deletion. The mutant was severely attenuated in virulence but not in colonization, demonstrating that OFS represents a novel virulence determinant of S. suis.