猪链球菌9型毒力基因的筛选及鉴定
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摘要
猪链球菌(Streptococcus suis)能引起猪脑膜炎、关节炎、败血症甚至死亡,也可导致生猪从业人员的感染和死亡,是一种重要的人畜共患病病原体。根据荚膜多糖的抗原性差异,猪链球菌分33个血清型,其中2型(SS2)分布最广,分离率最高,致病性最强。此外,9型(SS9)也是一个重要的致病血清型,在澳大利亚、荷兰、比利时、德国等国家SS9流行较广。近年来,在中国的发病猪中也经常分离SS9,且呈上升趋势。目前,猪链球菌的毒力因子的研究大都集中于SS2, SS9的相关研究很少。本研究采用抑制性差减杂交技术筛选及鉴定SS9毒力相关基因,并对部分基因的特性进行了较为深入的探索。
1抑制性差减杂交
为了获得毒力株所特有的基因片段,将SS9强毒株GZ0565与无毒株SH040917进行抑制性差减杂交。提取两株细菌基因组DNA, RsaI酶切回收。酶切的GZ0565(tester)基因组分别连接两个不同的接头.经过两轮杂交后,PCR扩增tester特有基因序列。扩增产物连接T载体转化大肠杆菌TOP10。随机挑取304个转化克隆,PCR分析结果显示其中286个为阳性克隆。
2可能毒力基因的筛选及功能预测
286个为阳性克隆的PCR产物变性固定于尼龙膜,分别与地高辛标记的GZ0565及SH040917酶切基因组DNA杂交。获得了61个毒力株GZ0565特异的基因片段。生物信息学分析结果表明这些片段编码30种不同的蛋白,包括编码溶血素相关蛋白、DNA核酸酶、类枯草杆菌丝氨酸蛋白酶、丝氨酸苏氨酸磷酸化酶等。
3可能毒力基因片段的分布分析
根据测序结果和同源性分析,选择14个具有代表性的差减片段设计引物,PCR检测这些片段在SS其他菌株上的分布。结果表明,这14个基因片段,在SS9菌株中,不同地区不同年份的临床分离株中均有广泛分布,无毒株SH040917全部阴性,屠宰分离株只有个别基因片段的分布；在SS2的致病菌株中有广泛分布。
4猪链球菌9型丝氨酸/苏氨酸磷酸化酶基因缺失株的构建及生物学特性分析
丝氨酸/苏氨酸磷酸化酶(serine/threonine phosphatase, STP)能够催化蛋白质的去磷酸化,与细胞内信号传递密切相关,且影响细菌的毒力和形态。为了进一步研究STP在SS9致病过程中的作用,本研究利用温度敏感型穿梭自杀质粒pSET4s定点敲除stp基因,获得基因缺失株△stp。将stp定向克隆至穿梭质粒pSET2中,构建互补质粒pSET2-STP,得到质粒介导的互补株C△stp.试验结果表明,缺失株△stp对HEp-2细胞的粘附能力明显下降,是野生株的粘附水平的68.8%,互补株C△stp的粘附能力比缺失株高,但是没有达到野生株的水平,是野生株的86.3%。缺失株△stp在全血中的存活能力明显减弱,野生株GZ0565的存活率是45.7%,缺失株△stp的存活率是23.4%,互补株C4stp的存活率是36.8%,比缺失株高,但是未达到野生株的水平。以CD1小鼠为模型比较了不同菌株的毒力,结果显示stp基因缺失后SS9毒力明显下降,缺失株△stp的LD50(1.93×107CFU)是野生株LD50(2.69×106CFU)的7倍,互补株C△stp的LDso为6.8×106CFU,是野生株的2.5倍。这些数据表明stp与SS9的致病性相关。
5猪链球菌9型溶血素相关蛋白基因缺失株的构建及生物学特性分析
溶血素(hemolysin)是细胞溶素家族的一个成员,能够使宿主细胞溶解的毒素,也是多种致病菌产生的重要致病因子。本研究前期鉴定出一个溶血素相关蛋白(Hemolysins and related proteins containing CBS domains, HlyC)基因,原核表达并纯化该蛋白,结果显示,rHlyC无溶血活性。为了进一步研究HlyC在SS9菌的致病过程中的作用,利用温度敏感型穿梭自杀质粒pSET4s定点敲除hlyC基因,获得基因缺失株△hlyC。将hlyC定向克隆至穿梭质粒pSET2中,构建互补质粒pSET2-HlyC,得到质粒介导的互补株pCHlyC。试验结果表明,hlyC缺失后,细菌溶解绵羊红细胞的能力无明显变化。突变株△hlyC对HEp-2细胞的粘附能力明显下降,是野生株的粘附水平的30.4%,互补株pCHlyC的粘附能力比缺失株高,但是未达到野生株的水平,是野生株的88%。突变株△hlyC在全血中的存活能力明显增强,野生株GZ0565的存活率是45.7%,突变株△hlyC的存活率是60.5%,互补株的存活率是48.2%。以CD1小鼠为模型比较了不同菌株的毒力,结果表明基因缺失后SS9毒力明显上升,野生株GZ0565的LD50(2.69×106CFU)比突变株△hlyC的LD50(3.79×105CFU)高7倍,对小鼠致病性增强,互补株LD50为1.49×106CFU。这些数据表明H1yC无溶血活性,与细菌的致病性密切相关。
6猪链球菌2型内皮翻转酶的免疫学特性分析
利用免疫蛋白组学方法,鉴定出猪链球菌2型江苏分离株HA9801具有免疫反应性的蛋白HM1。应用同源性比对、信号肽预测、跨膜区预测及亚定位预测等生物信息学方法对该蛋白进行分析,结果显示：同源性最高的蛋白为牙龈卟啉单胞菌的内肽酶(29%)；该蛋白序列中含有信号肽结构；无跨膜区,PCR检测该基因在SS2中的分布情况,并扩增出该蛋白的出信号肽以外的基因序列定向克隆到表达载体pET28a(+)中并转化大肠杆菌BL21(DE3).重组菌经IPTG诱导后的SDS-PAGE图谱在66kDa处出现融合蛋白的条带。Western blot表明,此重组蛋白rECE可被SPF微型猪抗SS2血清所识别,提示该蛋白可作为该菌的亚单位疫苗的候选物。纯化蛋白rECE能够黏附细胞外基质成分,间接免疫荧光试验证实该蛋白能够粘附上皮细胞,且该蛋白能抑制细菌对上皮细胞的粘附。rECE免疫小鼠后能够刺激机体产生特异性的抗体,能够提供70%的保护。
Streptococcus suis (S. suis) is a major swine pathogen responsible for a wide range of diseases,including septicaemia, meningitis, endocarditis, arthritis and even acute death. In addition to causing disease in pigs, it is also an important zoonotic agent that afflicts people in close contact with infected pigs or pork-derived products. Thirty-three types (1-31,33, and1/2) have been described based on capsular polysaccharides, type2(SS2) is the most frequently isolated and associated with disease, while S. suis type9(SS9) is also a prevalent type that is frequently isolated from diseased pigs in countries such as Australia, Holland, Belgium, and Germany. Most studies about virulence factors are based on SS2.Unlike those of SS2, little is known about SS9virulence factors.Suppression subtractive hybridization (SSH) was used between virulent strain GZ0565and avirulent strain SH040917. Thirty fragments of putative virulent genes were found by this method. The distributions of these fragments in other S. suis types isolates were detected. The role of virulence genes in SS9pathogenesis were investigated by using isogenic mutant.
1Suppression subtractive hybridization (SSH).
Suppression subtractive hybridization was carried out between virulent SS9strain GZ0565and avirulent strain SH040917in order to identify gene sequences unique to the virulent strains. The tester (GZ0565) and driver (SH040917) genomic DNAs were digested with Rsal. The tester DNA was then subdivided into two portions, each of which was ligated with a different adaptor provided. Two hybridizations were performed. The entire population of molecules was then subjected to PCR to amplify the tester-specific sequences. The PCR amplification product was cloned into PMD-18T simple vetor and transformed into E. coli TOP10competent cells. Three hundred and four subtractive clones were randomly picked.286colonies were confirmed as positive clones, but with no inserts in18colonies in total304colonies.
2Selection and identification of putative virulent genes
The inserts of286positive clones were amplified and arrayed on nylon membranes. Membranes were screened by hybridization with genomic DNA probe from tester and driver. Thirty gene sequences unique to virulent strain GZ0565were identified. These DNA fragments, containing putative virulence genes, encoded subtilisin-like serine protease, surface-anchored DNA nuclease, serine/threonine protein phosphatase, Hemolysins and related proteins containing CBS domains, GntR family regulatory protein, ABC transporter permease protein so on.
3Distribution of putative virulent genes in Streptococcus suis isolates
According to the results of DNA sequencing of postive clones and published SS2strain genomic sequence, PCR primers for14significant DNA fragments were designed and used for detection of the distribution of these fragments in S. suis isolates from different sources, types, regions.The results showed that these14DNA fragments were widely distributed in most SS9strains, specially those isolated from diseased pigs,yet were absent among the avirulent strain SH040917.However, other slaughter-house isolates possessed few the genes. Moreover these fragments could be detected in all virulent SS2islotates.In other types of S. suis, each type had a different distribution.
4.Construction of isogenic stp mutant strain and bionomics research of SS9WT and its derivatives
Serine/threonine phosphatases (STP) are the second largest class of enzymes that catalyze dephosphorylation of proteins, after protein tyrosine phosphatases. Serine/threonine phosphorylation/dephosphorylation is intimately linked with signaling events inside the cell. STP affects both the virulence and morphology of the bacteria. To investigate the role of stp in pathogenesis of SS9, an isogenic stp mutant (△stp) was constructed by allelic replacement using a temperature-sensitive S. suis-E. coli shuttle vector, pSET4s.The inact stp was cloned into shuttle vector pSET2to construct the recombinat plasmid pSET2-STP. Then the plasmid pSET2-STP transformed by electroporation into the△stp strain.The complementation strain designed C△stp. The adherence assy showed that the adherence to△stp strain to HEp-2cell was68.8%of WT, The adherence of complentation strain was86.3%of WT. The percent survival rate of the wild type parent strain was45.7%in whole blood. In contrast, the mutant was much more sensitive, with a percent survival rate of only 23.4%. The complentation strain C△stp was with a percent survival rate of36.8%. LD50values was2.69×106CFU per mouse for WT strain,1.93×107CFU per mouse for the mutant strain,6.8×106CFU per mouse for complentation strain C△stp.The LD50values of△stp was higher seven fold than that of wild type strain.The virulence of complementation strain C△stp was restored. Our data suggest that stp is involved in the pathogenesis of SS9.
5Construction of isogenic hlyC mutant strain and bionomics research of SS9WT and its derivatives
To investigate the role of hlyC in pathogenesis of SS9,an isogenic hlyC mutant(△hlyC) was constructed by allelic replacement using a temperature-sensitive S. suis-E. coli shuttle vector, pSET4s.The inact hlyC was cloned into shuttle vector pSET2to construct the recombinat plasmid pSET2-HlyC.Then the plasmid pSET2-HlyC transformed by electroporation into the△hlyC strain.The complementation strain designed pCHlyC. The adherence assy showed that the adherence to△hlyC strain to HEp-2cell was30.4%of WT, The adherence of complentation strain was88%of WT. The percent survival rate of the wild type strain was45.7%in whole blood,the mutant was with a percent survival rate of60.5%. The complentation strain was with a percent survival rate of48.2%.LD5o values was2.69×106CFU per mouse for WT strain,3.79×105CFU per mouse for the mutant strain,1.49×106CFU per mouse for complentation strain pCHlyC. The LD50values of mutant strain△hlyC was1/7of the wild type strain. The virulence of△hlyC was enhanced Complementation strain was restored. Our data suggest that hlyC is involved in the pathogenesis of SS9.
6The immunologic properties of streptococcus suis endothelin-converting enzyme
Streptococcus suis type2is a pathogen responsible for causing disease in both pigs and humans. Endothelin-converting enzyme (ECE) is an immunogenic protein of Streptococcus suis as well as a putative virulence factor. We expressed and purified ECE, which we demonstrate by Western blot is immunoreactive. In mice, ECE demonstrated a protective effect against S. suis infection. We demonstrate using ELISA assays that purified ECE can adhere to fibronectin and fibrinogen. We further show that ECE can bind to the surface of HEp-2cells via indirect immunofluorescent and adherence inhibition assays. Our results suggest that in addition to being a potential candidate subunit vaccine, ECE may also be important to S. suis pathogenesis.
1抑制性差减杂交
为了获得毒力株所特有的基因片段,将SS9强毒株GZ0565与无毒株SH040917进行抑制性差减杂交。提取两株细菌基因组DNA, RsaI酶切回收。酶切的GZ0565(tester)基因组分别连接两个不同的接头.经过两轮杂交后,PCR扩增tester特有基因序列。扩增产物连接T载体转化大肠杆菌TOP10。随机挑取304个转化克隆,PCR分析结果显示其中286个为阳性克隆。
2可能毒力基因的筛选及功能预测
286个为阳性克隆的PCR产物变性固定于尼龙膜,分别与地高辛标记的GZ0565及SH040917酶切基因组DNA杂交。获得了61个毒力株GZ0565特异的基因片段。生物信息学分析结果表明这些片段编码30种不同的蛋白,包括编码溶血素相关蛋白、DNA核酸酶、类枯草杆菌丝氨酸蛋白酶、丝氨酸苏氨酸磷酸化酶等。
3可能毒力基因片段的分布分析
根据测序结果和同源性分析,选择14个具有代表性的差减片段设计引物,PCR检测这些片段在SS其他菌株上的分布。结果表明,这14个基因片段,在SS9菌株中,不同地区不同年份的临床分离株中均有广泛分布,无毒株SH040917全部阴性,屠宰分离株只有个别基因片段的分布；在SS2的致病菌株中有广泛分布。
4猪链球菌9型丝氨酸/苏氨酸磷酸化酶基因缺失株的构建及生物学特性分析
丝氨酸/苏氨酸磷酸化酶(serine/threonine phosphatase, STP)能够催化蛋白质的去磷酸化,与细胞内信号传递密切相关,且影响细菌的毒力和形态。为了进一步研究STP在SS9致病过程中的作用,本研究利用温度敏感型穿梭自杀质粒pSET4s定点敲除stp基因,获得基因缺失株△stp。将stp定向克隆至穿梭质粒pSET2中,构建互补质粒pSET2-STP,得到质粒介导的互补株C△stp.试验结果表明,缺失株△stp对HEp-2细胞的粘附能力明显下降,是野生株的粘附水平的68.8%,互补株C△stp的粘附能力比缺失株高,但是没有达到野生株的水平,是野生株的86.3%。缺失株△stp在全血中的存活能力明显减弱,野生株GZ0565的存活率是45.7%,缺失株△stp的存活率是23.4%,互补株C4stp的存活率是36.8%,比缺失株高,但是未达到野生株的水平。以CD1小鼠为模型比较了不同菌株的毒力,结果显示stp基因缺失后SS9毒力明显下降,缺失株△stp的LD50(1.93×107CFU)是野生株LD50(2.69×106CFU)的7倍,互补株C△stp的LDso为6.8×106CFU,是野生株的2.5倍。这些数据表明stp与SS9的致病性相关。
5猪链球菌9型溶血素相关蛋白基因缺失株的构建及生物学特性分析
溶血素(hemolysin)是细胞溶素家族的一个成员,能够使宿主细胞溶解的毒素,也是多种致病菌产生的重要致病因子。本研究前期鉴定出一个溶血素相关蛋白(Hemolysins and related proteins containing CBS domains, HlyC)基因,原核表达并纯化该蛋白,结果显示,rHlyC无溶血活性。为了进一步研究HlyC在SS9菌的致病过程中的作用,利用温度敏感型穿梭自杀质粒pSET4s定点敲除hlyC基因,获得基因缺失株△hlyC。将hlyC定向克隆至穿梭质粒pSET2中,构建互补质粒pSET2-HlyC,得到质粒介导的互补株pCHlyC。试验结果表明,hlyC缺失后,细菌溶解绵羊红细胞的能力无明显变化。突变株△hlyC对HEp-2细胞的粘附能力明显下降,是野生株的粘附水平的30.4%,互补株pCHlyC的粘附能力比缺失株高,但是未达到野生株的水平,是野生株的88%。突变株△hlyC在全血中的存活能力明显增强,野生株GZ0565的存活率是45.7%,突变株△hlyC的存活率是60.5%,互补株的存活率是48.2%。以CD1小鼠为模型比较了不同菌株的毒力,结果表明基因缺失后SS9毒力明显上升,野生株GZ0565的LD50(2.69×106CFU)比突变株△hlyC的LD50(3.79×105CFU)高7倍,对小鼠致病性增强,互补株LD50为1.49×106CFU。这些数据表明H1yC无溶血活性,与细菌的致病性密切相关。
6猪链球菌2型内皮翻转酶的免疫学特性分析
利用免疫蛋白组学方法,鉴定出猪链球菌2型江苏分离株HA9801具有免疫反应性的蛋白HM1。应用同源性比对、信号肽预测、跨膜区预测及亚定位预测等生物信息学方法对该蛋白进行分析,结果显示：同源性最高的蛋白为牙龈卟啉单胞菌的内肽酶(29%)；该蛋白序列中含有信号肽结构；无跨膜区,PCR检测该基因在SS2中的分布情况,并扩增出该蛋白的出信号肽以外的基因序列定向克隆到表达载体pET28a(+)中并转化大肠杆菌BL21(DE3).重组菌经IPTG诱导后的SDS-PAGE图谱在66kDa处出现融合蛋白的条带。Western blot表明,此重组蛋白rECE可被SPF微型猪抗SS2血清所识别,提示该蛋白可作为该菌的亚单位疫苗的候选物。纯化蛋白rECE能够黏附细胞外基质成分,间接免疫荧光试验证实该蛋白能够粘附上皮细胞,且该蛋白能抑制细菌对上皮细胞的粘附。rECE免疫小鼠后能够刺激机体产生特异性的抗体,能够提供70%的保护。
Streptococcus suis (S. suis) is a major swine pathogen responsible for a wide range of diseases,including septicaemia, meningitis, endocarditis, arthritis and even acute death. In addition to causing disease in pigs, it is also an important zoonotic agent that afflicts people in close contact with infected pigs or pork-derived products. Thirty-three types (1-31,33, and1/2) have been described based on capsular polysaccharides, type2(SS2) is the most frequently isolated and associated with disease, while S. suis type9(SS9) is also a prevalent type that is frequently isolated from diseased pigs in countries such as Australia, Holland, Belgium, and Germany. Most studies about virulence factors are based on SS2.Unlike those of SS2, little is known about SS9virulence factors.Suppression subtractive hybridization (SSH) was used between virulent strain GZ0565and avirulent strain SH040917. Thirty fragments of putative virulent genes were found by this method. The distributions of these fragments in other S. suis types isolates were detected. The role of virulence genes in SS9pathogenesis were investigated by using isogenic mutant.
1Suppression subtractive hybridization (SSH).
Suppression subtractive hybridization was carried out between virulent SS9strain GZ0565and avirulent strain SH040917in order to identify gene sequences unique to the virulent strains. The tester (GZ0565) and driver (SH040917) genomic DNAs were digested with Rsal. The tester DNA was then subdivided into two portions, each of which was ligated with a different adaptor provided. Two hybridizations were performed. The entire population of molecules was then subjected to PCR to amplify the tester-specific sequences. The PCR amplification product was cloned into PMD-18T simple vetor and transformed into E. coli TOP10competent cells. Three hundred and four subtractive clones were randomly picked.286colonies were confirmed as positive clones, but with no inserts in18colonies in total304colonies.
2Selection and identification of putative virulent genes
The inserts of286positive clones were amplified and arrayed on nylon membranes. Membranes were screened by hybridization with genomic DNA probe from tester and driver. Thirty gene sequences unique to virulent strain GZ0565were identified. These DNA fragments, containing putative virulence genes, encoded subtilisin-like serine protease, surface-anchored DNA nuclease, serine/threonine protein phosphatase, Hemolysins and related proteins containing CBS domains, GntR family regulatory protein, ABC transporter permease protein so on.
3Distribution of putative virulent genes in Streptococcus suis isolates
According to the results of DNA sequencing of postive clones and published SS2strain genomic sequence, PCR primers for14significant DNA fragments were designed and used for detection of the distribution of these fragments in S. suis isolates from different sources, types, regions.The results showed that these14DNA fragments were widely distributed in most SS9strains, specially those isolated from diseased pigs,yet were absent among the avirulent strain SH040917.However, other slaughter-house isolates possessed few the genes. Moreover these fragments could be detected in all virulent SS2islotates.In other types of S. suis, each type had a different distribution.
4.Construction of isogenic stp mutant strain and bionomics research of SS9WT and its derivatives
Serine/threonine phosphatases (STP) are the second largest class of enzymes that catalyze dephosphorylation of proteins, after protein tyrosine phosphatases. Serine/threonine phosphorylation/dephosphorylation is intimately linked with signaling events inside the cell. STP affects both the virulence and morphology of the bacteria. To investigate the role of stp in pathogenesis of SS9, an isogenic stp mutant (△stp) was constructed by allelic replacement using a temperature-sensitive S. suis-E. coli shuttle vector, pSET4s.The inact stp was cloned into shuttle vector pSET2to construct the recombinat plasmid pSET2-STP. Then the plasmid pSET2-STP transformed by electroporation into the△stp strain.The complementation strain designed C△stp. The adherence assy showed that the adherence to△stp strain to HEp-2cell was68.8%of WT, The adherence of complentation strain was86.3%of WT. The percent survival rate of the wild type parent strain was45.7%in whole blood. In contrast, the mutant was much more sensitive, with a percent survival rate of only 23.4%. The complentation strain C△stp was with a percent survival rate of36.8%. LD50values was2.69×106CFU per mouse for WT strain,1.93×107CFU per mouse for the mutant strain,6.8×106CFU per mouse for complentation strain C△stp.The LD50values of△stp was higher seven fold than that of wild type strain.The virulence of complementation strain C△stp was restored. Our data suggest that stp is involved in the pathogenesis of SS9.
5Construction of isogenic hlyC mutant strain and bionomics research of SS9WT and its derivatives
To investigate the role of hlyC in pathogenesis of SS9,an isogenic hlyC mutant(△hlyC) was constructed by allelic replacement using a temperature-sensitive S. suis-E. coli shuttle vector, pSET4s.The inact hlyC was cloned into shuttle vector pSET2to construct the recombinat plasmid pSET2-HlyC.Then the plasmid pSET2-HlyC transformed by electroporation into the△hlyC strain.The complementation strain designed pCHlyC. The adherence assy showed that the adherence to△hlyC strain to HEp-2cell was30.4%of WT, The adherence of complentation strain was88%of WT. The percent survival rate of the wild type strain was45.7%in whole blood,the mutant was with a percent survival rate of60.5%. The complentation strain was with a percent survival rate of48.2%.LD5o values was2.69×106CFU per mouse for WT strain,3.79×105CFU per mouse for the mutant strain,1.49×106CFU per mouse for complentation strain pCHlyC. The LD50values of mutant strain△hlyC was1/7of the wild type strain. The virulence of△hlyC was enhanced Complementation strain was restored. Our data suggest that hlyC is involved in the pathogenesis of SS9.
6The immunologic properties of streptococcus suis endothelin-converting enzyme
Streptococcus suis type2is a pathogen responsible for causing disease in both pigs and humans. Endothelin-converting enzyme (ECE) is an immunogenic protein of Streptococcus suis as well as a putative virulence factor. We expressed and purified ECE, which we demonstrate by Western blot is immunoreactive. In mice, ECE demonstrated a protective effect against S. suis infection. We demonstrate using ELISA assays that purified ECE can adhere to fibronectin and fibrinogen. We further show that ECE can bind to the surface of HEp-2cells via indirect immunofluorescent and adherence inhibition assays. Our results suggest that in addition to being a potential candidate subunit vaccine, ECE may also be important to S. suis pathogenesis.
引文
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[1]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Vet Microbiol 2000 Oct 1;76(3):259-72.
[2]Hill JE, Gottschalk M, Brousseau R, Harel J, Hemmingsen SM, Goh SH. Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Vet Microbiol 2005 Apr 25;107(1-2):63-9.
[3]Allgaier A, Goethe R, Wisselink HJ, Smith HE, Valentin-Weigand P. Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits. J Clin Microbiol 2001 Feb;39(2):445-53.
[4]Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, Peperkamp K, Vecht U. Distribution of capsular types and production of muramidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis strains isolated from diseased pigs in seven European countries. Vet Microbiol 2000 Jun 1;74(3):237-48.
[5]Diatchenko L, Lau YF, Campbell AP, Chenchik A, Moqadam F, Huang B, et al. Suppression subtractive hybridization:a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc Natl Acad Sci U S A1996 Jun 11;93(12):6025-30.
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[8]Janke B, Hacker J, Blum-Oehler G Genetic characterization of the uropathogenic E. coli strain 536--a subtractive hybridization analysis. Adv Exp Med Biol 2000;485:53-6.
[9]Zhang YL, Ong CT, Leung KY. Molecular analysis of genetic differences between virulent and avirulent strains of Aeromonas hydrophila isolated from diseased fish. Microbiology 2000 Apr; 146 (Pt 4):999-1009.
[10]Sawada K, Kokeguchi S, Hongyo H, Sawada S, Miyamoto M, Maeda H, et al. Identification by subtractive hybridization of a novel insertion sequence specific for virulent strains of Porphyromonas gingivalis. Infect Immun 1999 Nov;67(11):5621-5.
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[1]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Vet Microbiol 2000 Oct 1;76(3):259-72.
[2]Hill JE, Gottschalk M, Brousseau R, Harel J, Hemmingsen SM, Goh SH. Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Vet Microbiol 2005 Apr 25;107(1-2):63-9.
[3]Allgaier A, Goethe R, Wisselink HJ, Smith HE, Valentin-Weigand P. Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits. J Clin Microbiol 2001 Feb;39(2):445-53.
[4]Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, Peperkamp K, Vecht U. Distribution of capsular types and production of muramidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis strains isolated from diseased pigs in seven European countries. Vet Microbiol 2000 Jun 1;74(3):237-48.
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[1]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Vet Microbiol 2000 Oct 1;76(3):259-72.
[2]Hill JE, Gottschalk M, Brousseau R, Harel J, Hemmingsen SM, Goh SH. Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Vet Microbiol 2005 Apr 25;107(1-2):63-9.
[3]Allgaier A, Goethe R, Wisselink HJ, Smith HE, Valentin-Weigand P. Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits. J Clin Microbiol 2001 Feb;39(2):445-53.
[4]Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, Peperkamp K, Vecht U. Distribution of capsular types and production of muramidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis strains isolated from diseased pigs in seven European countries. Vet Microbiol 2000 Jun 1;74(3):237-48.
[5]Jacobs AA, Loeffen PL, van den Berg AJ, Storm PK. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infect Immun 1994 May;62(5):1742-8.
[6]Smith HE, Vecht U, Gielkens AL, Smits MA. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infect Immun 1992 Jun;60(6):2361-7.
[7]Vecht U, Wisselink HJ, Jellema ML, Smith HE. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infect Immun 1991 Sep;59(9):3156-62.
[8]De Greeff A, Buys H, Verhaar R, Van Alphen L, Smith HE. Distribution of environmentally regulated genes of Streptococcus suis serotype 2 among S. suis serotypes and other organisms. J Clin Microbiol 2002 Sep;40(9):3261-8.
[9]XIU Fu-xiao LC-p. Detection of the virulence2associated genes of Streptococcus suis type 9 isolates in China and their protective efficacy in mice. Chinese Veterinary Science 2008;38(02):97-100.
[10]Wu Z, Zhang W, Lu C. Comparative proteome analysis of secreted proteins of Streptococcus suis serotype 9 isolates from diseased and healthy pigs. Microbial pathogenesis 2008 Sep;45(3):159-66.
[11]Takamatsu D, Osaki M, Sekizaki T. Construction and characterization of Streptococcus suis-Escherichia coli shuttle cloning vectors. Plasmid 2001 Mar;45(2):101-13.
[12]Takamatsu D, Osaki M, Sekizaki T. Thermosensitive suicide vectors for gene replacement in Streptococcus suis. Plasmid 2001 Sep;46(2):140-8.
[13]Vanier G, Segura M, Friedl P, Lacouture S, Gottschalk M. Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2. Infection and immunity 2004 Mar;72(3):1441-9.
[14]Bonifait L, de la Cruz Dominguez-Punaro M, Vaillancourt K, Bart C, Slater J, Frenette M, et al. The cell envelope subtilisin-like proteinase is a virulence determinant for Streptococcus suis. BMC microbiology; 10:42.
[15]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif 2001 Dec;25(4):402-8.
[16]Carvalho E, Barbosa AS, Gomez RM, Cianciarullo AM, Hauk P, Abreu PA, et al. Leptospiral TlyC is an extracellular matrix-binding protein and does not present hemolysin activity. FEBS Lett 2009 Apr 17;583(8):1381-5.
[17]Pan X, Ge J, Li M, Wu B, Wang C, Wang J, et al. The orphan response regulator CovR:a globally negative modulator of virulence in Streptococcus suis serotype 2. J Bacteriol 2009 Apr; 191 (8):2601-12.
[1]Hill JE, Gottschalk M, Brousseau R, Harel J, Hemmingsen SM, Goh SH. Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Vet Microbiol 2005 Apr 25;107(1-2):63-9.
[2]Yu H, Jing H, Chen Z, Zheng H, Zhu X, Wang H, et al. Human Streptococcus suis outbreak, Sichuan, China. Emerg Infect Dis 2006 Jun;12(6):914-20.
[3]Smith HE, Damman M, van der Velde J, Wagenaar F, Wisselink HJ, Stockhofe-Zurwieden N, et al. Identification and characterization of the cps locus of Streptococcus suis serotype 2:the capsule protects against phagocytosis and is an important virulence factor. Infect Immun 1999 Apr,67(4):1750-6.
[4]Vecht U, Wisselink HJ, Jellema ML, Smith HE. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infection and immunity 1991 Sep;59(9):3156-62.
[5]Jacobs AA, Loeffen PL, van den Berg AJ, Storm PK. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infect Immun 1994 May;62(5):1742-8.
[6]Okwumabua O, Persaud JS, Reddy PG Cloning and characterization of the gene encoding the glutamate dehydrogenase of Streptococcus suis serotype 2. Clin Diagn Lab Immunol 2001 Mar;8(2):251-7.
[7]Brassard J, Gottschalk M, Quessy S. Cloning and purification of the Streptococcus suis serotype 2 glyceraldehyde-3-phosphate dehydrogenase and its involvement as an adhesin. Vet Microbiol 2004 Aug 19;102(1-2):87-94.
[8]de Greeff A, Buys H, Verhaar R, Dijkstra J, van Alphen L, Smith HE. Contribution of fibronectin-binding protein to pathogenesis of Streptococcus suis serotype 2. Infect Immun 2002 Mar;70(3):1319-25.
[9]Winterhoff N, Goethe R, Gruening P, Rohde M, Kalisz H, Smith HE, et al. Identification and characterization of two temperature-induced surface-associated proteins of Streptococcus suis with high homologies to members of the Arginine Deiminase system of Streptococcus pyogenes. J Bacteriol 2002 Dec;184(24):6768-76.
[10]Smith HE, Buijs H, Wisselink HJ, Stockhofe-Zurwieden N, Smits MA. Selection of virulence-associated determinants of Streptococcus suis serotype 2 by in vivo complementation. Infect Immun 2001 Mar;69(3):1961-6.
[11]Fontaine MC, Perez-Casal J, Willson PJ. Investigation of a novel DNase of Streptococcus suis serotype 2. Infect Immun 2004 Feb;72(2):774-81.
[12]Osaki M, Takamatsu D, Shimoji Y, Sekizaki T. Characterization of Streptococcus suis genes encoding proteins homologous to sortase of gram-positive bacteria. J Bacteriol 2002 Feb;184(4):971-82.
[13]Segura M, Gottschalk M. Extracellular virulence factors of streptococci associated with animal diseases. Front Biosci 2004 May 1;9:1157-88.
[14]Baums CG, Kaim U, Fulde M, Ramachandran G, Goethe R, Valentin-Weigand P. Identification of a novel virulence determinant with serum opacification activity in Streptococcus suis. Infect Immun 2006 Nov;74(11):6154-62.
[15]Chen C, Tang J, Dong W, Wang C, Feng Y, Wang J, et al. A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates. PLoS ONE 2007;2:e315.
[16]Okwumabua O, Chinnapapakkagari S. Identification of the gene encoding a 38-kilodalton immunogenic and protective antigen of Streptococcus suis. Clin Diagn Lab Immunol 2005 Apr,12(4):484-90.
[17]Li Y, Martinez G, Gottschalk M, Lacouture S, Willson P, Dubreuil JD, et al. Identification of a surface protein of Streptococcus suis and evaluation of its immunogenic and protective capacity in pigs. Infect Immun 2006 Jan;74(1):305-12.
[18]Zhang W, Lu CP. Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2. Proteomics 2007 Dec;7(24):4468-76.
[19]Zhang W, Lu CP. Immunoproteomic assay of membrane-associated proteins of Streptococcus suis type 2 China vaccine strain HA9801. Zoonoses Public Health 2007;54(6-7):253-9.
[2]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Veterinary microbiology 2000 Oct 1;76(3):259-72.
[3]Yu H, Jing H, Chen Z, Zheng H, Zhu X, Wang H, et al. Human Streptococcus suis outbreak, Sichuan, China. Emerg Infect Dis 2006 Jun;12(6):914-20.
[4]Smith HE, Vecht U, Gielkens AL, Smits MA. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infection and immunity 1992 Jun;60(6):2361-7.
[5]Vecht U, Wisselink HJ, Jellema ML, Smith HE. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infection and immunity 1991 Sep;59(9):3156-62.
[6]de Greeff A, Buys H, Verhaar R, Dijkstra J, van Alphen L, Smith HE. Contribution of fibronectin-binding protein to pathogenesis of Streptococcus suis serotype 2. Infect Immun 2002 Mar;70(3):1319-25.
[7]Jacobs AA, Loeffen PL, van den Berg AJ, Storm PK. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infection and immunity 1994 May;62(5):1742-8.
[8]Smith HE, Damman M, van der Velde J, Wagenaar F, Wisselink HJ, Stockhofe-Zurwieden N, et al. Identification and characterization of the cps locus of Streptococcus suis serotype 2:the capsule protects against phagocytosis and is an important virulence factor. Infect Immun 1999 Apr;67(4):1750-6.
[9]Okwumabua O, Persaud JS, Reddy PG Cloning and characterization of the gene encoding the glutamate dehydrogenase of Streptococcus suis serotype 2. Clin Diagn Lab Immunol 2001 Mar;8(2):251-7.
[10]Brassard J, Gottschalk M, Quessy S. Cloning and purification of the Streptococcus suis serotype 2 glyceraldehyde-3-phosphate dehydrogenase and its involvement as an adhesin. Vet Microbiol 2004 Aug 19;102(1-2):87-94.
[11]Winterhoff N, Goethe R, Gruening P, Rohde M, Kalisz H, Smith HE, et al. Identification and characterization of two temperature-induced surface-associated proteins of Streptococcus suis with high homologies to members of the Arginine Deiminase system of Streptococcus pyogenes. J Bacteriol 2002 Dec;184(24):6768-76.
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[14]Osaki M, Takamatsu D, Shimoji Y, Sekizaki T. Characterization of Streptococcus suis genes encoding proteins homologous to sortase of gram-positive bacteria. J Bacteriol 2002 Feb;184(4):971-82.
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[16]Baums CG, Kaim U, Fulde M, Ramachandran G, Goethe R, Valentin-Weigand P. Identification of a novel virulence determinant with serum opacification activity in Streptococcus suis. Infect Immun 2006 Nov;74(11):6154-62.
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[1]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Vet Microbiol 2000 Oct 1;76(3):259-72.
[2]Hill JE, Gottschalk M, Brousseau R, Harel J, Hemmingsen SM, Goh SH. Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Vet Microbiol 2005 Apr 25;107(1-2):63-9.
[3]Allgaier A, Goethe R, Wisselink HJ, Smith HE, Valentin-Weigand P. Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits. J Clin Microbiol 2001 Feb;39(2):445-53.
[4]Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, Peperkamp K, Vecht U. Distribution of capsular types and production of muramidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis strains isolated from diseased pigs in seven European countries. Vet Microbiol 2000 Jun 1;74(3):237-48.
[5]Jacobs AA, Loeffen PL, van den Berg AJ, Storm PK. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infect Immun 1994 May;62(5):1742-8.
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[9]Yu WL LC, Wang GP, Lu CP. Pathogenic characteristics of Streptococcus suis type 2 and type 9 isolated from Guangdong province. Veterinary Science in China 2007;37(8):650-4.
[10]Wu Z, Zhang W, Lu C. Comparative proteome analysis of secreted proteins of Streptococcus suis serotype 9 isolates from diseased and healthy pigs. Microbial pathogenesis 2008 Sep;45(3):159-66.
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[14]Sawada K, Kokeguchi S, Hongyo H, Sawada S, Miyamoto M, Maeda H, et al. Identification by subtractive hybridization of a novel insertion sequence specific for virulent strains of Porphyromonas gingivalis. Infect Immun 1999 Nov;67(11):5621-5.
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[16]Fontaine MC, Perez-Casal J, Willson PJ. Investigation of a novel DNase of Streptococcus suis serotype 2. Infect Immun 2004 Feb;72(2):774-81.
[17]Hu Q, Liu P, Yu Z, Zhao G, Li J, Teng L, et al. Identification of a cell wall-associated subtilisin-like serine protease involved in the pathogenesis of Streptococcus suis serotype 2. Microbial pathogenesis 2010 Mar-Apr;48(3-4):103-9.
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[1]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Vet Microbiol 2000 Oct 1;76(3):259-72.
[2]Hill JE, Gottschalk M, Brousseau R, Harel J, Hemmingsen SM, Goh SH. Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Vet Microbiol 2005 Apr 25;107(1-2):63-9.
[3]Allgaier A, Goethe R, Wisselink HJ, Smith HE, Valentin-Weigand P. Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits. J Clin Microbiol 2001 Feb;39(2):445-53.
[4]Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, Peperkamp K, Vecht U. Distribution of capsular types and production of muramidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis strains isolated from diseased pigs in seven European countries. Vet Microbiol 2000 Jun 1;74(3):237-48.
[5]Diatchenko L, Lau YF, Campbell AP, Chenchik A, Moqadam F, Huang B, et al. Suppression subtractive hybridization:a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc Natl Acad Sci U S A1996 Jun 11;93(12):6025-30.
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[7]Janke B, Dobrindt U, Hacker J, Blum-Oehler G. A subtractive hybridisation analysis of genomic differences between the uropathogenic E. coli strain 536 and the E. coli K-12 strain MG 1655. FEMS Microbiol Lett 2001 May 15;199(1):61-6.
[8]Janke B, Hacker J, Blum-Oehler G Genetic characterization of the uropathogenic E. coli strain 536--a subtractive hybridization analysis. Adv Exp Med Biol 2000;485:53-6.
[9]Zhang YL, Ong CT, Leung KY. Molecular analysis of genetic differences between virulent and avirulent strains of Aeromonas hydrophila isolated from diseased fish. Microbiology 2000 Apr; 146 (Pt 4):999-1009.
[10]Sawada K, Kokeguchi S, Hongyo H, Sawada S, Miyamoto M, Maeda H, et al. Identification by subtractive hybridization of a novel insertion sequence specific for virulent strains of Porphyromonas gingivalis. Infect Immun 1999 Nov;67(11):5621-5.
[11]Yu WL LC, Wang GP, Lu CP. Pathogenic characteristics of Streptococcus suis type 2 and type 9 isolated from Guangdong province. Veterinary Science in China 2007;37(08):650-4.
[12]Zhao R SJ, Lu CP. Distributional Characteristics of Virulence-associated Gene of Streptococcus suis Strains Isolated from China. Journal of Shanghai Jiaotong University (Agricultural Science) 2006;24:495-8.
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[15]Smith HE, Vecht U, Gielkens AL, Smits MA. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infect Immun 1992 Jun;60(6):2361-7.
[16]Vecht U, Wisselink HJ, Jellema ML, Smith HE. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infect Immun 1991 Sep;59(9):3156-62.
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[18]XIU Fu-xiao Lu cheng-ping. Detection of the virulence-associated genes of Streptococcus suis type 9 isolates in China and their protective eff icacy in mice. Chinese Veterinary Science 2008;38(02):97-100.
[19]Wu Z, Zhang W, Lu C. Comparative proteome analysis of secreted proteins of Streptococcus suis serotype 9 isolates from diseased and healthy pigs. Microbial pathogenesis 2008 Sep;45(3):159-66.
[20]Fontaine MC, Perez-Casal J, Willson PJ. Investigation of a novel DNase of Streptococcus suis serotype 2. Infect Immun 2004 Feb;72(2):774-81.
[21]Hu Q, Liu P, Yu Z, Zhao G, Li J, Teng L, et al. Identification of a cell wall-associated subtilisin-like serine protease involved in the pathogenesis of Streptococcus suis serotype 2. Microbial pathogenesis 2010 Mar-Apr;48(3-4):103-9.
[1]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Vet Microbiol 2000 Oct 1;76(3):259-72.
[2]Hill JE, Gottschalk M, Brousseau R, Harel J, Hemmingsen SM, Goh SH. Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Vet Microbiol 2005 Apr 25;107(1-2):63-9.
[3]Allgaier A, Goethe R, Wisselink HJ, Smith HE, Valentin-Weigand P. Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits. J Clin Microbiol 2001 Feb;39(2):445-53.
[4]Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, Peperkamp K, Vecht U. Distribution of capsular types and production of muramidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis strains isolated from diseased pigs in seven European countries. Vet Microbiol 2000 Jun 1;74(3):237-48.
[5]Jacobs AA, Loeffen PL, van den Berg AJ, Storm PK. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infect Immun 1994 May;62(5):1742-8.
[6]Smith HE, Vecht U, Gielkens AL, Smits MA. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infect Immun 1992 Jun;60(6):2361-7.
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[8]De Greeff A, Buys H, Verhaar R, Van Alphen L, Smith HE. Distribution of environmentally regulated genes of Streptococcus suis serotype 2 among S. suis serotypes and other organisms. J Clin Microbiol 2002 Sep;40(9):3261-8.
[9]XIU Fu-xiao Lu Cheng-ping. Detection of the virulence-associated genes of Streptococcus suis type 9 isolates in China and their protective eff icacy in mice. Chinese Veterinary Science 2008;38(02):97-100.
[10]Wu Z, Zhang W, Lu C. Comparative proteome analysis of secreted proteins of Streptococcus suis serotype 9 isolates from diseased and healthy pigs. Microbial pathogenesis 2008 Sep;45(3):159-66.
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[20]Yu WL LC, Wang GP, Lu CP. Pathogenic characteristics of Streptococcus suis type 2 and type 9 isolated from Guangdong province. Veterinary Science in China 2007;37(08):650-4.
[21]Takamatsu D, Osaki M, Sekizaki T. Construction and characterization of Streptococcus suis-Escherichia coli shuttle cloning vectors. Plasmid 2001 Mar;45(2):101-13.
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[23]Vanier G, Segura M, Fried1 P, Lacouture S, Gottschalk M. Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2. Infection and immunity 2004 Mar;72(3):1441-9.
[24]Bonifait L, de la Cruz Dominguez-Punaro M, Vaillancourt K, Bart C, Slater J, Frenette M, et al. The cell envelope subtilisin-like proteinase is a virulence determinant for Streptococcus suis. BMC microbiology; 10:42.
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[1]Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis:the unresolved questions. Vet Microbiol 2000 Oct 1;76(3):259-72.
[2]Hill JE, Gottschalk M, Brousseau R, Harel J, Hemmingsen SM, Goh SH. Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Vet Microbiol 2005 Apr 25;107(1-2):63-9.
[3]Allgaier A, Goethe R, Wisselink HJ, Smith HE, Valentin-Weigand P. Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits. J Clin Microbiol 2001 Feb;39(2):445-53.
[4]Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, Peperkamp K, Vecht U. Distribution of capsular types and production of muramidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis strains isolated from diseased pigs in seven European countries. Vet Microbiol 2000 Jun 1;74(3):237-48.
[5]Jacobs AA, Loeffen PL, van den Berg AJ, Storm PK. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infect Immun 1994 May;62(5):1742-8.
[6]Smith HE, Vecht U, Gielkens AL, Smits MA. Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. Infect Immun 1992 Jun;60(6):2361-7.
[7]Vecht U, Wisselink HJ, Jellema ML, Smith HE. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infect Immun 1991 Sep;59(9):3156-62.
[8]De Greeff A, Buys H, Verhaar R, Van Alphen L, Smith HE. Distribution of environmentally regulated genes of Streptococcus suis serotype 2 among S. suis serotypes and other organisms. J Clin Microbiol 2002 Sep;40(9):3261-8.
[9]XIU Fu-xiao LC-p. Detection of the virulence2associated genes of Streptococcus suis type 9 isolates in China and their protective efficacy in mice. Chinese Veterinary Science 2008;38(02):97-100.
[10]Wu Z, Zhang W, Lu C. Comparative proteome analysis of secreted proteins of Streptococcus suis serotype 9 isolates from diseased and healthy pigs. Microbial pathogenesis 2008 Sep;45(3):159-66.
[11]Takamatsu D, Osaki M, Sekizaki T. Construction and characterization of Streptococcus suis-Escherichia coli shuttle cloning vectors. Plasmid 2001 Mar;45(2):101-13.
[12]Takamatsu D, Osaki M, Sekizaki T. Thermosensitive suicide vectors for gene replacement in Streptococcus suis. Plasmid 2001 Sep;46(2):140-8.
[13]Vanier G, Segura M, Friedl P, Lacouture S, Gottschalk M. Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2. Infection and immunity 2004 Mar;72(3):1441-9.
[14]Bonifait L, de la Cruz Dominguez-Punaro M, Vaillancourt K, Bart C, Slater J, Frenette M, et al. The cell envelope subtilisin-like proteinase is a virulence determinant for Streptococcus suis. BMC microbiology; 10:42.
[15]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif 2001 Dec;25(4):402-8.
[16]Carvalho E, Barbosa AS, Gomez RM, Cianciarullo AM, Hauk P, Abreu PA, et al. Leptospiral TlyC is an extracellular matrix-binding protein and does not present hemolysin activity. FEBS Lett 2009 Apr 17;583(8):1381-5.
[17]Pan X, Ge J, Li M, Wu B, Wang C, Wang J, et al. The orphan response regulator CovR:a globally negative modulator of virulence in Streptococcus suis serotype 2. J Bacteriol 2009 Apr; 191 (8):2601-12.
[1]Hill JE, Gottschalk M, Brousseau R, Harel J, Hemmingsen SM, Goh SH. Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Vet Microbiol 2005 Apr 25;107(1-2):63-9.
[2]Yu H, Jing H, Chen Z, Zheng H, Zhu X, Wang H, et al. Human Streptococcus suis outbreak, Sichuan, China. Emerg Infect Dis 2006 Jun;12(6):914-20.
[3]Smith HE, Damman M, van der Velde J, Wagenaar F, Wisselink HJ, Stockhofe-Zurwieden N, et al. Identification and characterization of the cps locus of Streptococcus suis serotype 2:the capsule protects against phagocytosis and is an important virulence factor. Infect Immun 1999 Apr,67(4):1750-6.
[4]Vecht U, Wisselink HJ, Jellema ML, Smith HE. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infection and immunity 1991 Sep;59(9):3156-62.
[5]Jacobs AA, Loeffen PL, van den Berg AJ, Storm PK. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infect Immun 1994 May;62(5):1742-8.
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