马链球菌兽疫亚种纤连蛋白结合蛋白功能片段的确定及免疫保护试验
|
摘要
马链球菌兽疫亚种(Streptococcus equi subsp．zooepidemicus)对集约化养猪业的发展危害严重，同时对养猪业的相关从业人员的健康具有潜在威胁。能引起猪和人的脑膜炎、败血症、关节炎、肺炎、及突发性死亡，是重要的人兽共患病病原。
纤连蛋白(fibronectin，Fn)是由α和β链组成的一种二聚体糖蛋白，由多种类型的细胞表达产生，Fn在动物体内以可溶形式存在于血浆及各种体液中，以不溶形式存在于细胞外基质及细胞表面。前者总称血浆Fn，后者总称细胞Fn。
纤连蛋白结合蛋白(fibronectin-binding protein，FNZ)是链球菌一种重要的表面蛋白和毒力因子，是链球菌建立感染所依附的重要的表面分子之一，该菌是重要的黏附素。本试验在分子水平上对马链球菌兽疫亚种FNZ蛋白的功能片段进行了研究，为该菌的致病机制和基因工程疫苗的研制进行了有益的探索。
根据已经发表的马链球菌兽疫亚种纤连蛋白结合蛋白的基因序列，设计和合成一对引物，并以ATCC35246株的基因组为模板，通过PCR技术，扩增出缺失信号肽的FNZ基因，并定向克隆至PMD19-T载体中。酶切鉴定正确后，对克隆片段进行序列测定，其长度为1895bp。利用DNAstar软件，比较所测序列与不同来源链球菌的纤连蛋白序列的同源性，该序列与已经发表的马链球菌兽疫亚种VTU211菌株FNZ基因的同源性为89．9％，氨基酸同源性为84．4％，其中突变部位较多，而且中间有111个碱基缺失。与马链球菌马亚种的同源性为78％，氨基酸同源性为44．1％，与其他链球菌的同源性较低。
根据ATCC35246的FNZ基因序列，设计和合成五对引物，用PCR方法分别扩增出FNZ基因的4-277bp、4-808bp、592-1134bp、895-1615bp区间和全长的基因片段。将扩增片段双酶切后用T4 DNA连接酶定向克隆于融合表达载体pET-32a(+)的相应酶切位点。构建pFNZ(2-91)、pFNZ(2-268)、pFNZ(197-378)、pFNZ(299-538)和pFNZ重组质粒，对阳性插入片段进行酶切测序鉴定，结果表明pFNZ(2-91)、pFNZ(2-268)、pFNZ(197-378)、pFNZ(299-538)和pFNZ的插入序列与ATCC35246FNZ的相应序列完全一致。将重组质粒转化大肠杆菌BL21，经IPTG诱导表达，表达产物大小分别为31、50、40、45、84kD，与预测结果一致。
采用配基印迹结合试验确定FNZ上Fn的结合部位，结果表明pFNZ(2-268)、pFNZ(197-378)、pFNZ(299-538)和pFNZ与人的Fn结合。据此推断在FNZ基因的277-808bp、895-1134bp，即197-268aa、299-378aa之间有Fn的线性结合位点。
将含有Fn线性结合部位的重组质粒细菌进行表达，SDS-PAGE检测，结果表明表达的蛋白位于上清之中，以His亲和层析柱纯化表达蛋白，将纯化好的蛋白与ISA206佐剂1：1进行乳化后免疫ICR小鼠，融合蛋白免疫方式为pFNZ(2-268)、pFNZ(299-538)和pFNZ(2-268)+pFNZ(299-538)，以0．2ml(1．0×10~8cell／ml)ATCC35246强毒株攻击后，小鼠的存活率分别为20％、30％和30％，证实所表达的蛋白具有一定的保护性，为马链球菌兽疫亚种重要的保护性抗原。
Streptococcus equi subsp.zooepidemicus made substantial economic losses for pig industry and became a substantial threat to human health especially those involved in the pig industry. they are worldwide zoonotic pathogens and lead to many different diseases characterized by meningitis, septicemia, arthritis, endocarditis and may cause sudden dealth in pig or human.
Fn is a large dimeric glycoprotein composed of aand (3 polypeptide chains, which is generated by several cells.Fn is present in a soluble form in hematoplasma and erevy body fluids and in a fibrillar form in the extracellular matrix of connective tissue. The former is called by hematoplasma Fn, and the latter is called by cell Fn.
Fibronectin-binding protein (FNZ) is an important surface protein and virulenceassociated factor of Streptococcus equi subsp.zooepidemicus, which is to mediate substrate adhesion of eukaryotic cells.It is one of the main adhension of SEZ.In the present study,at the molecular levels,we investigated the virulence factors of FNZ in order to get new insights into the pathogenic mechanism and new prevention methods against Streptococcus equi subsp.zooepidemicus.
Based on the sequence of FNZ published on the genbank of Streptococcus equi subsp.zooepidemicus,FNZ gene was amplified from genomic DNA of Streptococcus equi subsp.zooepidemicus ATCC35246 strain by polymerase chain reaction(PCR), then the amplified gene was cloned into pMD-19 vector.The recombinant plasmid was verified by restriction endonuclease analysis and nucleotide sequencing.Nucleotide sequencing analysis revealed a 1895bp fragment of FNZ gene of strain ATCC35246,the accession number of this sequence to GenBank is DQ363208.sequence comparison with other published FNZ gene of Streptococci showed that the FNZ gene nucleotide sequence was 89.9% identical to that of Streptococcus equi subsp. zooepidemicus VTU211 strain, and 78 %identical to that of Streptococcus equi subsp. equi, and the FNZ protein sequence was 84.4% identical to that of Streptococcus equi subsp.zooepidemicus VTU211 strain, 44.1 % identical to that of Streptococcus equi subsp. equi. It is low homology with other streptococcus. More mutation exists and 111bp is absent in FNZ gene.
Based on the sequence of ATCC35246 FNZ gene, five gene fragments of FNZ gene beween 4-277bp、4-808bp、592-1134bp、895-1615bp and 4-1716bp were amplified from the genomic DNA of SEZ by PCR.Then the amplified fragments were cloned into the plasmid of pET-32a (+),the recombinant plasmids of pFNZ (2-91)、pFNZ (2-268)、pFNZ (197-378)、pFNZ (299-538) and pFNZ were verified by restriction endonuclease analysis and nucleotide sequencing.These recombinant plasmids were trasfomated into its host E.coli strains BL21, recombinant proteins of 31、50、45、25、84kD were highly expressed after induced by IPTG respectively. SDS-PAGE analysis showed that the recombinant proteins had the molecular weight as expected.
Western ligand affinity blot assay were used with recombinant fusion protein pFNZ (2-91)、pFNZ(2-268)、pFNZ(197-378)、pFNZ(299-538)and pFNZ,respectively.The results showed that the recombinant fusion protein pFNZ (2-268)、pFNZ (197-378)、pFNZ (299-538) and pFNZ can bind hFn. Therefore, it is speculated that the epitopes are present in FNZ gene 277-808bp and 895-1134bp, the FNZ protein have linear Fn-binding domain between 197-268 and 299-378 amino acid residue.
The BL21 was induced by IPTG to over express, which contains the linear Fn-binding domain recombinant plasmids, SDS-PAGE showed that the fusion protein exist in supernatant. The fusion protein was purified by affinity chromatograph column, and emulsionized by ISA206. The ICR mice were immunized with the purified recombinant protein of pFNZ(2-268)、pFNZ(299-538)和pFNZ (2-268)+pFNZ(299-538) respectively, the 20%、30% and 30% of mice were survival after challenge with Streptococcus equi subsp.zooepidemicus strain ATCC35246. It demonstrated that the recombinant protein was a protective antigen and maybe a critical functional fragment of FNZ.
纤连蛋白(fibronectin，Fn)是由α和β链组成的一种二聚体糖蛋白，由多种类型的细胞表达产生，Fn在动物体内以可溶形式存在于血浆及各种体液中，以不溶形式存在于细胞外基质及细胞表面。前者总称血浆Fn，后者总称细胞Fn。
纤连蛋白结合蛋白(fibronectin-binding protein，FNZ)是链球菌一种重要的表面蛋白和毒力因子，是链球菌建立感染所依附的重要的表面分子之一，该菌是重要的黏附素。本试验在分子水平上对马链球菌兽疫亚种FNZ蛋白的功能片段进行了研究，为该菌的致病机制和基因工程疫苗的研制进行了有益的探索。
根据已经发表的马链球菌兽疫亚种纤连蛋白结合蛋白的基因序列，设计和合成一对引物，并以ATCC35246株的基因组为模板，通过PCR技术，扩增出缺失信号肽的FNZ基因，并定向克隆至PMD19-T载体中。酶切鉴定正确后，对克隆片段进行序列测定，其长度为1895bp。利用DNAstar软件，比较所测序列与不同来源链球菌的纤连蛋白序列的同源性，该序列与已经发表的马链球菌兽疫亚种VTU211菌株FNZ基因的同源性为89．9％，氨基酸同源性为84．4％，其中突变部位较多，而且中间有111个碱基缺失。与马链球菌马亚种的同源性为78％，氨基酸同源性为44．1％，与其他链球菌的同源性较低。
根据ATCC35246的FNZ基因序列，设计和合成五对引物，用PCR方法分别扩增出FNZ基因的4-277bp、4-808bp、592-1134bp、895-1615bp区间和全长的基因片段。将扩增片段双酶切后用T4 DNA连接酶定向克隆于融合表达载体pET-32a(+)的相应酶切位点。构建pFNZ(2-91)、pFNZ(2-268)、pFNZ(197-378)、pFNZ(299-538)和pFNZ重组质粒，对阳性插入片段进行酶切测序鉴定，结果表明pFNZ(2-91)、pFNZ(2-268)、pFNZ(197-378)、pFNZ(299-538)和pFNZ的插入序列与ATCC35246FNZ的相应序列完全一致。将重组质粒转化大肠杆菌BL21，经IPTG诱导表达，表达产物大小分别为31、50、40、45、84kD，与预测结果一致。
采用配基印迹结合试验确定FNZ上Fn的结合部位，结果表明pFNZ(2-268)、pFNZ(197-378)、pFNZ(299-538)和pFNZ与人的Fn结合。据此推断在FNZ基因的277-808bp、895-1134bp，即197-268aa、299-378aa之间有Fn的线性结合位点。
将含有Fn线性结合部位的重组质粒细菌进行表达，SDS-PAGE检测，结果表明表达的蛋白位于上清之中，以His亲和层析柱纯化表达蛋白，将纯化好的蛋白与ISA206佐剂1：1进行乳化后免疫ICR小鼠，融合蛋白免疫方式为pFNZ(2-268)、pFNZ(299-538)和pFNZ(2-268)+pFNZ(299-538)，以0．2ml(1．0×10~8cell／ml)ATCC35246强毒株攻击后，小鼠的存活率分别为20％、30％和30％，证实所表达的蛋白具有一定的保护性，为马链球菌兽疫亚种重要的保护性抗原。
Streptococcus equi subsp.zooepidemicus made substantial economic losses for pig industry and became a substantial threat to human health especially those involved in the pig industry. they are worldwide zoonotic pathogens and lead to many different diseases characterized by meningitis, septicemia, arthritis, endocarditis and may cause sudden dealth in pig or human.
Fn is a large dimeric glycoprotein composed of aand (3 polypeptide chains, which is generated by several cells.Fn is present in a soluble form in hematoplasma and erevy body fluids and in a fibrillar form in the extracellular matrix of connective tissue. The former is called by hematoplasma Fn, and the latter is called by cell Fn.
Fibronectin-binding protein (FNZ) is an important surface protein and virulenceassociated factor of Streptococcus equi subsp.zooepidemicus, which is to mediate substrate adhesion of eukaryotic cells.It is one of the main adhension of SEZ.In the present study,at the molecular levels,we investigated the virulence factors of FNZ in order to get new insights into the pathogenic mechanism and new prevention methods against Streptococcus equi subsp.zooepidemicus.
Based on the sequence of FNZ published on the genbank of Streptococcus equi subsp.zooepidemicus,FNZ gene was amplified from genomic DNA of Streptococcus equi subsp.zooepidemicus ATCC35246 strain by polymerase chain reaction(PCR), then the amplified gene was cloned into pMD-19 vector.The recombinant plasmid was verified by restriction endonuclease analysis and nucleotide sequencing.Nucleotide sequencing analysis revealed a 1895bp fragment of FNZ gene of strain ATCC35246,the accession number of this sequence to GenBank is DQ363208.sequence comparison with other published FNZ gene of Streptococci showed that the FNZ gene nucleotide sequence was 89.9% identical to that of Streptococcus equi subsp. zooepidemicus VTU211 strain, and 78 %identical to that of Streptococcus equi subsp. equi, and the FNZ protein sequence was 84.4% identical to that of Streptococcus equi subsp.zooepidemicus VTU211 strain, 44.1 % identical to that of Streptococcus equi subsp. equi. It is low homology with other streptococcus. More mutation exists and 111bp is absent in FNZ gene.
Based on the sequence of ATCC35246 FNZ gene, five gene fragments of FNZ gene beween 4-277bp、4-808bp、592-1134bp、895-1615bp and 4-1716bp were amplified from the genomic DNA of SEZ by PCR.Then the amplified fragments were cloned into the plasmid of pET-32a (+),the recombinant plasmids of pFNZ (2-91)、pFNZ (2-268)、pFNZ (197-378)、pFNZ (299-538) and pFNZ were verified by restriction endonuclease analysis and nucleotide sequencing.These recombinant plasmids were trasfomated into its host E.coli strains BL21, recombinant proteins of 31、50、45、25、84kD were highly expressed after induced by IPTG respectively. SDS-PAGE analysis showed that the recombinant proteins had the molecular weight as expected.
Western ligand affinity blot assay were used with recombinant fusion protein pFNZ (2-91)、pFNZ(2-268)、pFNZ(197-378)、pFNZ(299-538)and pFNZ,respectively.The results showed that the recombinant fusion protein pFNZ (2-268)、pFNZ (197-378)、pFNZ (299-538) and pFNZ can bind hFn. Therefore, it is speculated that the epitopes are present in FNZ gene 277-808bp and 895-1134bp, the FNZ protein have linear Fn-binding domain between 197-268 and 299-378 amino acid residue.
The BL21 was induced by IPTG to over express, which contains the linear Fn-binding domain recombinant plasmids, SDS-PAGE showed that the fusion protein exist in supernatant. The fusion protein was purified by affinity chromatograph column, and emulsionized by ISA206. The ICR mice were immunized with the purified recombinant protein of pFNZ(2-268)、pFNZ(299-538)和pFNZ (2-268)+pFNZ(299-538) respectively, the 20%、30% and 30% of mice were survival after challenge with Streptococcus equi subsp.zooepidemicus strain ATCC35246. It demonstrated that the recombinant protein was a protective antigen and maybe a critical functional fragment of FNZ.
引文
1 陈耀春．中国动物疫病志[M]．北京：科技出版社，1993：230-233．
2 何小娟，黄炽明．猪链球菌病[J]．中国动物检疫,2002,19(9)：42-44．
3 何孔旺，陆承平．猪链球菌2型的致病性与毒力因子[J]．中国兽医科技,2000,30(9)：17-18．
4 王继春，何孔旺，何家惠，等．猪链球菌2型动物致病性试验研究[J]．中国兽医科技,2001，31(8)：27-29．
5 蔡宝祥．家畜传染病学(第2版)[M]．北京：农业出版社，1991，186-190．
6 韩谦，郑世军，赵德明，等，译．默克兽医手册(第7版)[M]．北京：中国农业大学出版社，1997：310-312．
7 姜天童，徐涤平，方雨玲，等．猪链球菌病多价苗安全性和免疫性试验[1]．中国兽医杂志,2001，37(8)：21—22．
8 姜天童，徐涤平，方雨玲，等．猪源致病性链球菌分群鉴定及血清学等调查[J]．中国兽医杂志，1999,25(11)：8—10．
9 倪艳秀，何孔旺，王继春，等．检测猪链球菌2型胞外因子(EF)的PCR方法的建立[J]．中国人兽共患病杂志,2001，17(4)：57-59．
10 Robertson I DBlackmore D K, Hampson D J, et al. A longitudinal study of natural infenction of piglets with Streptococcus suis type 1 and 2[J].Epidemiol Infect.1991, 107. 119-126
11 Williams A E, Blackmore W F, Alexander T J L. Amurine model of Streptococcus suis type 2 meningitis in pigs[J]. Res Vet Sci, 1988,45:394-395
12 Enright M R, Alexander T J, Clifton-Hadley F A. Role of houseflies (Musca domestica) in the epidemiology of Streptococcus suis type 2[J]. Vet Rec, 1987,121:132-133
13 Robertson l D, Blackmore D K. Prevalence of Streptococcus suis type 1 and 2 in domestic pigs in Australia and New Zealand[J]. Vet Rec, 1989, 124:391-394
14 Dee S A, Carlson A R, Winkelman N L, et al.Effect of management practices on the Streptococcus suis carrier rate in nuesery swine[J]. J Am Vet Med Assoc,1993, 203:295-299
15 Power S B. Streptococcus suis type 2 in fection in pigs[J]. Vet Rec, 1978,102(10): 215-216
16 Sanford S E.Streptococcus suis:a strategic update . In: Proceeding of the annual meeting of the American association of swine Practitioners[J]. Des Moines, 1989, 193-195
17 Sanford S E and Tilker M E. Streptococcus suis type 2 associated diseases in swine: observations of a one year study[J]. J Ame Vet Med Ass, 1982,181 : 673-676
18 Clifton-Hadley F A, Alexander T J . Diagnosis of Streptococcus suis infection in pigs[J]. In E Boden(ed), Swine Practice. 1991, 115-126
19 Sihvonen L, Kurl D N and Henrichsen J. Streptococcus suis isolated from pigs in Finland[J]. Acta Vet Scand, 1988, 29:9-13
20 Kataoka Y, Sugimoto C, Nakazawa M, et al. The epidemiological tudies of Streptococcus suis infection in Japan from 1987 to 1991 [J]. J Vet Med Sci, 1993,55:623-626
21 Reams R Y, Harrington D D, Glickman L T, et al. Multiple serotypes and strains of Streptococcus suis in naturally infected swine herds[J]. J Vet Diagn Invest, 1996, 8:119-121
22 Health P J, Hunt B W, Duff J P, et al. Streptococcus suis type 14 as a cause of pig disease in the UK[J]. Vet Rec, 1996, 139:450-451
23 Moore B O, Bryans J T1 Antigenic classification of group C animal streptococci[J]. J Am Vet Med Assoc, 1969,155:416-420
24 Field H I, Buntain D and Done J T.Studies on piglet mortality.l.Streptococcal meningitis and arthritis.Vet Rec, 1954,66:453-455
25 范荣俊，吴海萍．猪败血性链球菌病的诊断和防治[J]．中国兽医杂志,2001，37(11)：40-41．
26 李连喜．猪链球菌病的防治[J]．中国兽医杂志，1998,24(5)：45．
27 王森．猪链球菌的发病特点和防治方法[J]．中国动物检疫,2002,19(10)：35．
28 龙清孟．猪链球菌病的防治[J]．贵州畜牧兽医,2002,26(6)：30．
29 蒋岩，刘爱武．猪链球菌病的诊治[J]．中国兽医科技,2002,32(10)：38—39．
30 牛桂玲，徐淑华．猪链球菌病的诊断和防治[J]．中国兽医杂志,2001，37(12)：24-25．
31 方东艳，王满定，孙勇涛，等．猪败血性链球菌病的诊治[J]．动物医学进展,2002,23(5)：112．
32 苏定国，宋培林．猪链球菌诊断报告[J]．中国兽医杂志，1990，16(3)：34-35．
33 张宝龙，张国忠．猪链球菌病的诊断[J]．中国兽医杂志，1996,22(8)：37．
34 周国慧．猪败血性链球菌病的诊疗报告[J]．贵州畜牧兽医，1999,23(2)：19-20．
35 严章政．汪德军，余斌，等．猪链球菌病的诊治报告[J]．中国兽医杂志,2001，37(1)：34-35．
36 孙业辉，赵荣．猪败血性链球病的防治[J]．中国兽医杂志,2002,38(12)：621动物医学进展 2003年第24卷第5期(总第127期)
37 Timoney J F, Walker J, Zhou M , et all Cloning and sequence analysis of a protective M-like protein gene from Streptococcus equi subsp zooepidemicus (J) .lnfect Immun, 1995,63 (4) :1440 - 1445.
38 Stattas J J,Feder I,Okwumabua O et al.Streptococcus suis: past snd present.Vet Res commun, 1997,21(6):381-407.Review
39 Ream R Y, Glickman L T, Harrington D D,et al.Streptococcus suis infenction in swine:a retrospective study of 256 Cases.part 2.Clinical signs,gross and microscopic lesions,and coexsting microorga nisms. J Vet Diagn Invest, 1994,6(3):326-334
40 Galina L, Collins J E Pijoin C.Porcine Streptococcus suis in Minnesota.J Vet Diagn Invest, 1992,4:195-196
41 Robertson I D.Blackmore D K,Hanpsond J.et al.A longitudinal study of natural infection of piglets with Streptococcus suis type land2.Epidemiol Infect, 1991,107:119-126
42 范红结，陆承平，唐家琪．马链球菌兽疫亚种类M 蛋向的基因克隆、序列分析及其在猪源链球菌的检测[J]．微生物学报，2004，44(5)：617-620
43 Berry A M, Paton J C.Sequence heterogeneity of PsaA, a 37kilodalton putative adhesin essential for virulence of St reptococcus pneumoniae[J]. Infect Immun ,1996,64:5255-5262.
44 Janulczyk R, Pallon J, Bjoirck L.Identification and characterization of a St reptococcus pyogenes ABC transporter with multiple specificity for metal cations[J]. Mol Microbiol, 1999,34 : 596 -606.
45 Kolenbrander P E, Andersen R N, Baker R A, et al.The adhesion-associated sca operon in Streptococcus gordonii encodes an inducible high-affinity ABC transporter for Mn2 + uptake[J]. J Bacteriol, 1998,180 : 290-295.
46 Caballero A R, Lottenberg R, Johnston K.Cloning ,expressing ,sequence analysis, and characteriza
tion of Streptokinase secreted by porcine and equine isolates of Streptococcus equisimilis[J]. Infect Immun ,1999,67 (12) : 6478-6486.
47 Boyle M D P, Lottenberg R.Plasminogen activation by invasive human pathogens[J]. Thromb Haemost, 1997,77:1 - 10.
48 McCoy H E, Broder C C, Lottenberg R..Streptokinases produced by pathogenic group C streptococci demonstrate species specificity plasminogen activation[J]. J Infect Dis, 1991 , 164:515 -521.
49 Benkirane R, Gottschalk M,Dubreuil J D. Identification of Streptococcus suis 60-kDa heat-shock protein using western blotting[J]. Microbiol Lett, 1997,153 (2):379-385.
50 Serhir B,Higgins R, Foiry B. Detection of immunoglobulin-G-binding proteins in Streptococcus suis[J].J Gen Microbiol, 1993,139 (12):2953-2958.
51 Mamo W, Froman G, Sundtts A, et al .Binding of fibronectin, fibrinogen and type Ⅱ collagen to streptococci isolated from bovinemastitis[J]. Microb Pathog, 1987,2:417 - 424.
52 Jonsson H , Lindmark H , Guss B. A protein G-related cell surface protein in Streptococcus zooepidemicus[J]. Infect Immun ,1995 ,63 (8): 2968-2975.
53 Nygren P A , Eliasson M , Palmcrantz E , et al.Analysis and use of the serum albumin binding domains of streptococcal protein G[J]. J Mol Recognlt, 1988 ,1 :69 - 74.
54 Valentin-Weigand P , Traore M Y, Blobel H , et al .Role of cxemacroglobulin in phagocytosis of group A and C streptococci [J].FEMS Microbiol Lett, 1990, 70 :321-324.
55 Myhre E B , Kuusela P.Binding of human fibronectin to group A ,C , and G streptococci [J]. Infect Immun ,1983, 40: 29-34.
56 Lindmark H , Jacobsson K, Frykberg L , et al.Fibronectin-binding protein of Streptococcus equi subsp zooepidemicus[J]. Infect Immun ,1996 , 64 (10): 3993-3999.
57 Hong K. Identification and characterization of a novel Fibronectin-binding protein gene from S.zooepi demicus strain VTU 211[J].FEMS Immunol Med Microbiol, 2005 ,45 (2) :231-237.
58 范红结，陆承平．马链球菌兽疫亚种毒力因子[J]．中国人兽共患病学报，2006，22(3)：279-280．
59 Swildens B, Stockhofe-Zurwieden N, van der Meulen J, et al. Intestinal translocation of Streptococcus suis type 2 EF + in pigs[J]. VetMicrobiol,2004,103 (1 - 2): 29-33.
60 Segura M, Gottschalk M, Olivier M. Encapsulated Streptococcus suis inhibits activation of signaling pathways involved in phagicytosis[J]. Infect Immun, 2004, 72 (9): 5322-5330.
61 Vanier G, Segura M, Friedl P, et al. Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2 [J]. Infect Immun, 2004, 72 (3): 1441-1449.
62 Segura M, Vadeboncoeur N, Gottschalk M. CD4-dependent and independent cytokine and chenokine production by human THP-1 monocytes stimulated by Streptococcus suis capsula type 2 [J]. Clin Exp Immunol,2002,127 (2): 243-254.
63 Bergey's .Manual of Systematic Bacteriology[M]. 1986. 1070
64 陆承平主编．兽医微生物学第三版[M]．中国农业出版社．211-212
65 Mogollon JD, Pijoan C, Murtaugh MP. Characterization of prototype and clinically defined strains of Streptococcus suis by genomic fingerprinting [J]. Clin Microbiol 1990, 28(11):2462-2466.
66 Devriese L A, Ceyssencs K, Hommez J, et al .Characteristics of different Streptococcus suis ecovars and description of simplified identification[J]. Vet Microbiol, 1991, 26: 141-150.
67 Perch B,Pedersen K B, Henrichsen J. Serology of capsulated streptococci pathogenic for pigs: six new serotypes of Streptococcus suis [J] .Clin Microbiol, 1983, 17(6):993-996.
68 Tikkanen K, Hayrinen J, Pelkonen S. Immunoblot analysis of bacterial polysaccharides: application to the type-specific polysaccharides of Streptococcus suis and Streptococcus agalactiae [J]. Immunol Methods 1995, 1;187(2):233-244
69 I.Soedannanto,F.H.Pasaribu,I.W.T.Wibawan,and C.LAmmler. Identification and Molecular Characterization of Serological Group C Streptococci Isolated from Diseased Pigs and Monkeys in Indonesia
70 Ana I Vela, Joaquin Goyache, Carmen Tarradas . Analysis of genetic diversity of streptococcus suis clinical isolates fron pigs in spain by pulsed-field gel electrophoresis[J] . Clin Microbio , 2003, 41(6):2498-2502.
71 Hampson D J, Trott D J, Clarke IL, et al. Population structure of Australian isolates of Streptococcus suis[J]. J Clin Microbiol. 1993, 31:2895-2900
72 Mwaniki C G, Robertson I D, Trott D J. Clonal analysis and virulence of Australian isolates of Streptococcus suis type 2[J]. Epidemiol Infect, 1994,113:321-334.
73 Smith H E, Rijnsburger M, Stockhofe-Zurwieden, et al. Virulent strains of Streptococcus suis type 2 and highly virulent strains of Streptococcus suis type 1 can be recognized by a unique ribotype profile[J]. J Clin Microbiol, 1997,35:1049-1053
74 Beaudoin M, Harel J ,Higgins R, et al. Molecular analysis of isolates of Streptococcus suis type 2 by restriction-endonuclease digested DNA separated on SDS-PAGE and by hybridization with rRNA probe[J]. J Gen Microbiol, 1992a, 138:2639-2645
75 Staats J J, Plattner B L, Nirtfeld j, et al. Use of ribotyping and hemolysin activity to identify highly virulent Streptococcus suis type 2 isolates[J]. J Clin Microbiol, 1998,36:15-18
76 蔡宝祥．家畜传染病学[M]．北京：中国农业出版社，1998．93
1 陆承平，兽医微生物．第三版．北京：中国农业出版社，2001，209
2 Nicholson M..Ferdinand LL.,Sampson JS.Benin A.Balter S..Pinto SWL.Dowell SF.,Facklam RR,.Carlone GM,and Beall B.Analysis of immunoreactivity to a Streptococcus equi subsp.zooepidemicus M-Iike protein to confirm an outbreak of poststreptococcal glomerulonephritis and sequences of M-like proteins from isolates obtained from different host species.J.Clin.Microbiol.,2000;38:4126-4130
3 Arends J P,Zanen H C.Meningitis caused by Streptococcus suis in human.Rev Infect Dis,1988,10:131-137
4 Stattas J J.Feder I.Okwumabua O,et al.Streptococcus Suis:past and present.Vet Res commun, 1997,21 (6):381 -407.Review
5 Knodler LA,Celli J and Finaly BB.Pathogenic trickery:deception of host cell processes.Nature Rev Mol Cell Biol 2001,2:578-588
6 谢怡敏．整合素系统对人精子顶体反应的作用．四川生理科学杂志，2003，25(1)：29-32．
7 沈建箴，吕连煌．血浆纤连蛋白水平在急性白血病中的变化．中华医院感染学杂志，2000；10
8 Liaw L, Skinner MP, Raines EW, et al.The adhesive and migratory ef fects of osteopontic are mediad via distinct cell surface integrins.J Clin Invest, 1995, 95 (2) :713-724.
9 Hynes RO.Interin:versatility, modulation and signaling in cell adhesion.Cell, 1992, 69 (1) :11-25.
10 Sebag J, Balazs EA.Morphology and ultrastructure of human vitreous fibers.Invest Ophthalmol Vis Sci, 1989, 30:1867-1871.
11 Baekalow FJ, and Schwarzbauer JE. Localization of the major hepair-binding site in fibronectin. J Biol Chem 1991, 266:7812-7812
12 Armstrong PB, Armstrong M T. Intercellular invasion and the organizatoinal stablity of tissues: a role for fibronectin. Biochim. Biophys. Acta.2000,470(2):09
13 Yamamoto Y , Tsutsumi Y , M ayumi T. M olecular design of bioconjugated cell adhesion peptide with a water—soluble polymeric modifier for enhancement of antimetastatic effect. Curr Drug Targets, 2002 ,3(2): 123
14 Ruoslahti E. Fibronectin and ltrs Receptor. Annu. Rev. Biochem , 1988,57:375-413
15 Mostafavi-Pour Z, Askari JA, Whittard JD and Humphries MJ. Identification of a novel heparin-binding site in the alternatively spliced ⅢCS region of fibronectin: roles of integrins and proteoglycans in cell adhesion to fibronectin splice variants. Matrix Biol. 2001, 20:63-73.
16 Hahn L and Yamada K. Identification and isolation of a collagen-binding fragement of the adhesive glycoprotein fibronectin.Proc Natl Acad Sci USA 1979, 76:1160-1163
17 朱肖奇，秦廷武．细胞黏附基础与肌腱组织工程．生物医学工程学杂志，2004，21(2)：329．332
18 Chothia C, Jones EY.The Moleuclar Structure of Cell Adhesion Moleuclars.Annu.Rev. Biochem, 1997,66(8):3
19 Lin H,Lal R.Clegg DO.Imaging and Mapping Heparin-Bind Sites on Single Fibronectin M olecules with Atom ic Force M iroscopy. Biochemistry, 2000,39(3):9
20 Patel RS, Odermatt E, Schwarzbauer JE and Hynes RO. Organization of the fibronectin gene provides evidence for exon shuffling during evolution. EMBO J. 1987, 6: 2565-2572.
1 Collazos J, Echevarria M J, Ayarza R, et al. Streptococcus zooepidemicus septicarthritis :case report and reviewof group C streptococcal arthritis. Clin Infect Dis, 1992,16:744 - 746.
2 Barnham M, Ljunggren A, Mcintyre M. Human infection with Streptococcus zooepidemicus (Lancefield group C) : three case reports. Epidem Infect, 1987,98:183 - 190.
3 Hynes, R. O. 1990. Fibronectins. Springer Verlag, New York.
4 Mosher, D. F. 1989. Fibronectin. Academic Press Inc., San Diego, Calif.
5 Ruoslahti, E. E.G.Hayman, and M. D. Pierschbacher. 1985. Extracellular matrices and cell adhesion. Arteriosclerosis 5:581-594.
6 J 萨姆布鲁克，EF弗里奇，T曼尼阿蒂斯。金冬雁，孟黎枫等译．分子克隆实验指南。第二版．北京：科学出版社，1993
7 Chhatwal GS.Anchorless adhesions and invasions of Gram-positive bacteria:a new class of virulence factors.Trends Microbiol..2002;10:205-208
8 Flock, J.-I., G. Froman, K. Jonsson, B. Guss, C. Signas, B. Nilsson, G.Raucci, M. Hook, T. Wadstrom, and M. Lindberg. 1987. Cloning and expression of the gene for a fibronectin-binding protein from Staphylococcus aureus. EMBO J. 6:2351-2357.
9 Jonsson, K., C. Signas, H.-P. Muller, and M. Lindberg. 1991. Two different genes encode fibronectin binding proteins in Staphylococcus. The complete nucleotide sequence and characterization of the second gene. Eur. J. Biochem. 202:1041-1048.
10 Signas, C, G. Raucci, K. Jonsson, P.-E. Lindgren, G. M. Anantharamaiah.M. Hook, and M. Lindberg. 1989. Nucleotide sequence of the gene for a fibronectin-binding protein from Staphylococcus aureus: use of this peptide sequence in the synthesis of biologically active peptides. Proc. Natl. Acad.Sci. USA 86:699-703.
11 Sela, S., A. Aviv, A. Tovi, 1. Burstein, M. G. Caparon, and E. Hanski. 1993.Protein F: an adhesin of Streptococcus pyogenes binds fibronectin via two distinct domains. Mol. Microbiol. 10:1049-1055.
12 Courtney, H. S., Y. Li, J. B. Dale, and D. L. Hasty. 1994. Cloning, sequencing and expression of a fibronectin/fibrinogen-binding protein from group A streptococci. Infect. Immun. 62:3937-3946.
13 Chen, C. C, and P. P. Cleary. 1990. Complete nucleotide sequence of the streptococcal C5a peptidase gene of Streptococcus pyogenes. J. Biol. Chem.265:3161-3167.
14 Whatmore AM.Streptococcus pyogenes sclB encodes aputative hypervariable surface protein with a collagen-like repetitive structure.Microbiol.,2001;147:419-429.
15 Greeff A,Herma B,Robin V.et al.Contribution of fibronectin-binding protein to pathogenesis of Streptococcus suis Serotype2.1nfect.lmmun.,2002;70:1319-1325.
16 Shigetada K,Eiji E,Yutaka T,et al.Systemic and mucosal immunizations with fibronectin-binding protein FBP54 induce protective immune responses against Streptococcus pyogenes challenge in mice.lnfect.Immun.,2001;69:924-930.
1 Greeff A , Herma B , Robin V , et al. Cont ribution of fibronectin-binding protein to pat hogenesis of Streptococcus suis serotype2[J]. Infect Immun ,2000 ,68 (2) :637-643.
2 Finlay B B , Cossart P. Exploitation of mammalian host cell functions by bacterial pathogens [J]. Science, 1997,276:718-725.
3 Greeff A , Herma B , Robin V , et al. Contribution of fibronectin-binding protein to pathogenesis of Streptococcus suis serotype 2[J]. Infect Immun ,2000,68 (2) :637-643.
4 Joh D,wann ER,Kreikemeyer B,Speziale P,H66k MRole of fibronectin-binding MSCRAMMs in bacterial adherence and entry into mammalian cell.Matrix Biol., 1999; 18:211-223
5 peacock SJ,lina G,Etienne J,and Foster TJ.Staphylococcus schleiferi subsp. Schleiferi expresses a fibronectin-binding protein.Infect.Immun.,1999;67:4272-4275
6 Allignet J.Aubert S,Dyke KGH,and Solh N. Staphylococcus caprae strains carry determinants known to be involved in pathogenicity:a gene encoding an autolysin-binding fibronectin and the ica operon involved in biofilm formation.Infect.Immun.,2001;69:712-718
7 Chia JS.Yeh CY,and Chen JY.Identification of a fibronectin binding protein from Streptococcus mutans. Infect.Immun.2000;68:1864-1870
8 Christie J.McNab R.and Jenkinson HF.Expressin of fibronectin-binding protein FbpA modulates adhesion in Streptococcus gordonii.Microbiol.,2002; 148:1615-1625
9 Latorre M, Alvalez M, Fernandez J M ,et al. A case of meningitis due to Streptococcus zooepidemicus[J]. Clin Infect Dis ,1993 ,17 :932-933.
10 Martinez2Luengas F, Inclan G M, Paster A , et al. Endocarditis due to Streptococcus zooepidemicus[J]. Can Med Assoc J ,1982,127 :13.
11 Collazos J , Echevarria M J , Ayarza R ,et al . Streptococcus zooepidemicus septic arthritis : case report and review of group C streptococcal art hritis[J]. Clin Infect Dis , 1992 , 16 : 744-746.
12 Rose H D, Allen J R ,and Witte G. Streptococcus zooepidemicus (group C) pneumonia in a human [J]. J Clin Microbiol, 1980,11; 76-78.
13 Barham M, Thorton T J, Lange K. Nephritis caused by S treptococcus zooepidemicus (Lancefield group C) [J]. Lancet Ⅰ,1983 ,945-948.
14 Center for disease control. Group C streptococcal infections associated with eating homemade cheese [J]. New Mexico Morbid Mortal Weekly Rep, 1983 ,32 :510-516.
15 陆承平．兽医微生物学(第三版)[M]．北京：中国农业出版社,2001，204-212．
16 姚火春，陈国强，陆承平．猪链球菌1998分离株病原特性鉴定[J]．南京农业大学学报，1999，22 (2)：67—70．
17 刘佩红、沈素芳、于永康，等．上海地区猪源链球菌病原特性鉴定[J]．中国兽医学报．2001．21(1)：42-46．
18 萨姆布鲁克，EF弗里奇，T曼尼阿蒂斯。金冬雁，孟黎枫等译．分子克隆实验指南。第二版．北京：科学出版社，1993
19 Chhatwal GS.Anchorless sdhesins and invasions of Gram-positive bacteria:a new class of virulence factors.Trends Microbiol..2002;10:205-208.
1 Areds,J.P.,and H.C.Zanen.Meningitis caused by Streptococcus suis in humans.Rev.Infect Dis., 1988; 10:131 - 137
2 Chanter,N.,P.W.Jones,and T.J.L.Alexander.Meningitis in pigs caused by Streptococcus suis aspecularive review.Vet.Microbiol., 1993;36:39-55
3 Gottschalk M,&Segura M.The pathogenesis of the meningitis caused by streptococcus suis:the unresolved questions.Vet.Microbiol.,2000;76:259-272
4 Barnham M, Ljunggren A, Mcintyre M. Human infection with Streptococcus zooepidemicus (Lancefield group C) : three case reports. Epidem Infect, 1987,98:183 - 190.
5 范红结，陆承平，唐家琪．马链球菌兽疫亚种类M基因和猪链球菌2型mrp基因片段的融合表达及仔猪免疫试验．南京农业大学学报，2003，26(4)：78-81．
6 Sharp M W, Prince MJ ,Gibbens J. Streptococcus equi subsp, zooepidemicus infection and bovine mastitis. Vet Rec, 1995,137: 128-129.
7 陆承平．兽医微生物学．第三版．北京：中国农业出版社，2001，233-246．
8 Field H I, Buntain D and Done J T.Studies on piglet mortality.Ⅰ. Streptococcal meningitis and arthritis. Vet Rec, 1954,66:453-455
9 Berry A M , Paton J C.Sequence heterogeneity of PsaA , a 37kilodalton putative adhesin essential for virulence of St reptococcus pneumoniae[i]. Infect Immun ,1996 , 64 :5255 - 5262.
10 Janulczyk R, Pallon J , Bjoirck L. Identification and characterization of a St reptococcus pyogenes ABC transporter with multiple specificity for metal cations[J]. Mol Microbiol, 1999 , 34 : 596 -606.
11 Kolenbrander P E , Andersen R N , Baker R A , et al.The adhesion-associated sca operon in Streptococcus gordonii encodes an inducible high-affinity ABC transporter for Mn2 + uptake[J]. J Bacteriol, 1998,180:290-295.
12 Caballero A R, Lottenberg R, Johnston K.Cloning .expressing .sequence analysis , and characterization of Streptokinase secreted by porcine and equine isolates of Streptococcus equisimilis[J]. Infect Immun. 1999 , 67 (12): 6478-6486.
13 Benkirane R, Gottschalk M.Dubreuil J D. Identification of Streptococcus suis 60-kDa heat-shock protein using western blotting[J]. Microbiol Lett, 1997,153(2):379-385.
14 Knodler LA.Celli J and Finaly BB.Pathogenic trickery deception of host cell processes.Nature Rev Mol Cell Biol 2001,2:578-588
15 Greeff A.Herma B.Robin V,et al.Contribution of fibronectin-binding protein to pathogenesis of Streptococcus suis capsular type2.Infect.Immun.,2002;70:1319-1325.
16 Myhre E B , Kuusela P.Binding of human fibronectin to group A ,C , and G streptococci [J]. Infect Immun, 1983, 40:29-34.
17 Walker,J.A.and Timoney, J.F.(1998) Molecular basis of variation in protective SzP proteins of Streptococcus zooepidemicus.Am.J.Vet.Res.59,1129-1133.
1 Hasty D LItzbak ofek,Courtney H S,et al.Multiple adhesions of streptococci.Infect Immun, 1992,60(6):2174-2152
2 Beachey E H,Simpson W A.The adherence of group A streptococci to oropharyn-geal cells:The lipoteichoic acid adhesion and fibronectin receptor. Infection, 1982,10:107-101
3 Tamura GS , Rubens CE . Group B Streptococci(GBS) adhere to a variant of fibronectin attached to a solid phase [J]. Molecular Micobiology 1995,15:581-589.
4 Christie J,McNab R, Jenkinson HE Expression of fibronectin-binding protein FbpA modulates adhesion in streptococcus gordonii [J]. Microbiol. 2002,148:1615-1625.
5 Lindmark H, Jacobsson K,Frykberg L,and Guss B.Fibronectin-Binding Protein of Streptococcus equi subsp.zooepidemicus.Infect.Immun.,l996;64:3993-3999
6 Myhre EB and Kuusela P.Binding of Human Fibronectin to Group A,C and G Streptococci.Infect.Immun., 1983;40:29-34
7 Lindmark H,Jonsson P,Engvall EO and Guss B.Pulsed-field gel electrophoresis and distribution of the genes zag and fnz in isolates of Streptococcus equi.Res.Vet.Sci., 1999;66:93-99.
8 Hynes,R.O. 1990.Fibronectins.SpringerVerlag,NewYork.
9 H.S.Courtney,D.L.Hasty,Y.Li,H.C.Chiang,J.L.Thacker,J.B.Dale,Serum opacity factor is a major fibronectin-binding protein and a virulence determinant of M type2 Streptococcus pyosenes,Mol.Microbiol.32(1999)89-98.
10 Y.Terao,S.Kawabata,M.Nakata,I.Nakagawa,S.Hamada,Molecular characterization of a novel fibronectin-binding protein of Streptococcus pyogenes strains isolated from toxic shock-like syndrome patients,J.Biol.Chem.277(2002)47428-47435.
11 Kyongsu Hong. Identification and characterization of a novel fibronectin-binding protein protein fron Streptococcus equi subspecies zooepidemicus strain VTU211.[J]. Immunology and Medical Microbiology.2005,45:231-237.
2 何小娟，黄炽明．猪链球菌病[J]．中国动物检疫,2002,19(9)：42-44．
3 何孔旺，陆承平．猪链球菌2型的致病性与毒力因子[J]．中国兽医科技,2000,30(9)：17-18．
4 王继春，何孔旺，何家惠，等．猪链球菌2型动物致病性试验研究[J]．中国兽医科技,2001，31(8)：27-29．
5 蔡宝祥．家畜传染病学(第2版)[M]．北京：农业出版社，1991，186-190．
6 韩谦，郑世军，赵德明，等，译．默克兽医手册(第7版)[M]．北京：中国农业大学出版社，1997：310-312．
7 姜天童，徐涤平，方雨玲，等．猪链球菌病多价苗安全性和免疫性试验[1]．中国兽医杂志,2001，37(8)：21—22．
8 姜天童，徐涤平，方雨玲，等．猪源致病性链球菌分群鉴定及血清学等调查[J]．中国兽医杂志，1999,25(11)：8—10．
9 倪艳秀，何孔旺，王继春，等．检测猪链球菌2型胞外因子(EF)的PCR方法的建立[J]．中国人兽共患病杂志,2001，17(4)：57-59．
10 Robertson I DBlackmore D K, Hampson D J, et al. A longitudinal study of natural infenction of piglets with Streptococcus suis type 1 and 2[J].Epidemiol Infect.1991, 107. 119-126
11 Williams A E, Blackmore W F, Alexander T J L. Amurine model of Streptococcus suis type 2 meningitis in pigs[J]. Res Vet Sci, 1988,45:394-395
12 Enright M R, Alexander T J, Clifton-Hadley F A. Role of houseflies (Musca domestica) in the epidemiology of Streptococcus suis type 2[J]. Vet Rec, 1987,121:132-133
13 Robertson l D, Blackmore D K. Prevalence of Streptococcus suis type 1 and 2 in domestic pigs in Australia and New Zealand[J]. Vet Rec, 1989, 124:391-394
14 Dee S A, Carlson A R, Winkelman N L, et al.Effect of management practices on the Streptococcus suis carrier rate in nuesery swine[J]. J Am Vet Med Assoc,1993, 203:295-299
15 Power S B. Streptococcus suis type 2 in fection in pigs[J]. Vet Rec, 1978,102(10): 215-216
16 Sanford S E.Streptococcus suis:a strategic update . In: Proceeding of the annual meeting of the American association of swine Practitioners[J]. Des Moines, 1989, 193-195
17 Sanford S E and Tilker M E. Streptococcus suis type 2 associated diseases in swine: observations of a one year study[J]. J Ame Vet Med Ass, 1982,181 : 673-676
18 Clifton-Hadley F A, Alexander T J . Diagnosis of Streptococcus suis infection in pigs[J]. In E Boden(ed), Swine Practice. 1991, 115-126
19 Sihvonen L, Kurl D N and Henrichsen J. Streptococcus suis isolated from pigs in Finland[J]. Acta Vet Scand, 1988, 29:9-13
20 Kataoka Y, Sugimoto C, Nakazawa M, et al. The epidemiological tudies of Streptococcus suis infection in Japan from 1987 to 1991 [J]. J Vet Med Sci, 1993,55:623-626
21 Reams R Y, Harrington D D, Glickman L T, et al. Multiple serotypes and strains of Streptococcus suis in naturally infected swine herds[J]. J Vet Diagn Invest, 1996, 8:119-121
22 Health P J, Hunt B W, Duff J P, et al. Streptococcus suis type 14 as a cause of pig disease in the UK[J]. Vet Rec, 1996, 139:450-451
23 Moore B O, Bryans J T1 Antigenic classification of group C animal streptococci[J]. J Am Vet Med Assoc, 1969,155:416-420
24 Field H I, Buntain D and Done J T.Studies on piglet mortality.l.Streptococcal meningitis and arthritis.Vet Rec, 1954,66:453-455
25 范荣俊，吴海萍．猪败血性链球菌病的诊断和防治[J]．中国兽医杂志,2001，37(11)：40-41．
26 李连喜．猪链球菌病的防治[J]．中国兽医杂志，1998,24(5)：45．
27 王森．猪链球菌的发病特点和防治方法[J]．中国动物检疫,2002,19(10)：35．
28 龙清孟．猪链球菌病的防治[J]．贵州畜牧兽医,2002,26(6)：30．
29 蒋岩，刘爱武．猪链球菌病的诊治[J]．中国兽医科技,2002,32(10)：38—39．
30 牛桂玲，徐淑华．猪链球菌病的诊断和防治[J]．中国兽医杂志,2001，37(12)：24-25．
31 方东艳，王满定，孙勇涛，等．猪败血性链球菌病的诊治[J]．动物医学进展,2002,23(5)：112．
32 苏定国，宋培林．猪链球菌诊断报告[J]．中国兽医杂志，1990，16(3)：34-35．
33 张宝龙，张国忠．猪链球菌病的诊断[J]．中国兽医杂志，1996,22(8)：37．
34 周国慧．猪败血性链球菌病的诊疗报告[J]．贵州畜牧兽医，1999,23(2)：19-20．
35 严章政．汪德军，余斌，等．猪链球菌病的诊治报告[J]．中国兽医杂志,2001，37(1)：34-35．
36 孙业辉，赵荣．猪败血性链球病的防治[J]．中国兽医杂志,2002,38(12)：621动物医学进展 2003年第24卷第5期(总第127期)
37 Timoney J F, Walker J, Zhou M , et all Cloning and sequence analysis of a protective M-like protein gene from Streptococcus equi subsp zooepidemicus (J) .lnfect Immun, 1995,63 (4) :1440 - 1445.
38 Stattas J J,Feder I,Okwumabua O et al.Streptococcus suis: past snd present.Vet Res commun, 1997,21(6):381-407.Review
39 Ream R Y, Glickman L T, Harrington D D,et al.Streptococcus suis infenction in swine:a retrospective study of 256 Cases.part 2.Clinical signs,gross and microscopic lesions,and coexsting microorga nisms. J Vet Diagn Invest, 1994,6(3):326-334
40 Galina L, Collins J E Pijoin C.Porcine Streptococcus suis in Minnesota.J Vet Diagn Invest, 1992,4:195-196
41 Robertson I D.Blackmore D K,Hanpsond J.et al.A longitudinal study of natural infection of piglets with Streptococcus suis type land2.Epidemiol Infect, 1991,107:119-126
42 范红结，陆承平，唐家琪．马链球菌兽疫亚种类M 蛋向的基因克隆、序列分析及其在猪源链球菌的检测[J]．微生物学报，2004，44(5)：617-620
43 Berry A M, Paton J C.Sequence heterogeneity of PsaA, a 37kilodalton putative adhesin essential for virulence of St reptococcus pneumoniae[J]. Infect Immun ,1996,64:5255-5262.
44 Janulczyk R, Pallon J, Bjoirck L.Identification and characterization of a St reptococcus pyogenes ABC transporter with multiple specificity for metal cations[J]. Mol Microbiol, 1999,34 : 596 -606.
45 Kolenbrander P E, Andersen R N, Baker R A, et al.The adhesion-associated sca operon in Streptococcus gordonii encodes an inducible high-affinity ABC transporter for Mn2 + uptake[J]. J Bacteriol, 1998,180 : 290-295.
46 Caballero A R, Lottenberg R, Johnston K.Cloning ,expressing ,sequence analysis, and characteriza
tion of Streptokinase secreted by porcine and equine isolates of Streptococcus equisimilis[J]. Infect Immun ,1999,67 (12) : 6478-6486.
47 Boyle M D P, Lottenberg R.Plasminogen activation by invasive human pathogens[J]. Thromb Haemost, 1997,77:1 - 10.
48 McCoy H E, Broder C C, Lottenberg R..Streptokinases produced by pathogenic group C streptococci demonstrate species specificity plasminogen activation[J]. J Infect Dis, 1991 , 164:515 -521.
49 Benkirane R, Gottschalk M,Dubreuil J D. Identification of Streptococcus suis 60-kDa heat-shock protein using western blotting[J]. Microbiol Lett, 1997,153 (2):379-385.
50 Serhir B,Higgins R, Foiry B. Detection of immunoglobulin-G-binding proteins in Streptococcus suis[J].J Gen Microbiol, 1993,139 (12):2953-2958.
51 Mamo W, Froman G, Sundtts A, et al .Binding of fibronectin, fibrinogen and type Ⅱ collagen to streptococci isolated from bovinemastitis[J]. Microb Pathog, 1987,2:417 - 424.
52 Jonsson H , Lindmark H , Guss B. A protein G-related cell surface protein in Streptococcus zooepidemicus[J]. Infect Immun ,1995 ,63 (8): 2968-2975.
53 Nygren P A , Eliasson M , Palmcrantz E , et al.Analysis and use of the serum albumin binding domains of streptococcal protein G[J]. J Mol Recognlt, 1988 ,1 :69 - 74.
54 Valentin-Weigand P , Traore M Y, Blobel H , et al .Role of cxemacroglobulin in phagocytosis of group A and C streptococci [J].FEMS Microbiol Lett, 1990, 70 :321-324.
55 Myhre E B , Kuusela P.Binding of human fibronectin to group A ,C , and G streptococci [J]. Infect Immun ,1983, 40: 29-34.
56 Lindmark H , Jacobsson K, Frykberg L , et al.Fibronectin-binding protein of Streptococcus equi subsp zooepidemicus[J]. Infect Immun ,1996 , 64 (10): 3993-3999.
57 Hong K. Identification and characterization of a novel Fibronectin-binding protein gene from S.zooepi demicus strain VTU 211[J].FEMS Immunol Med Microbiol, 2005 ,45 (2) :231-237.
58 范红结，陆承平．马链球菌兽疫亚种毒力因子[J]．中国人兽共患病学报，2006，22(3)：279-280．
59 Swildens B, Stockhofe-Zurwieden N, van der Meulen J, et al. Intestinal translocation of Streptococcus suis type 2 EF + in pigs[J]. VetMicrobiol,2004,103 (1 - 2): 29-33.
60 Segura M, Gottschalk M, Olivier M. Encapsulated Streptococcus suis inhibits activation of signaling pathways involved in phagicytosis[J]. Infect Immun, 2004, 72 (9): 5322-5330.
61 Vanier G, Segura M, Friedl P, et al. Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2 [J]. Infect Immun, 2004, 72 (3): 1441-1449.
62 Segura M, Vadeboncoeur N, Gottschalk M. CD4-dependent and independent cytokine and chenokine production by human THP-1 monocytes stimulated by Streptococcus suis capsula type 2 [J]. Clin Exp Immunol,2002,127 (2): 243-254.
63 Bergey's .Manual of Systematic Bacteriology[M]. 1986. 1070
64 陆承平主编．兽医微生物学第三版[M]．中国农业出版社．211-212
65 Mogollon JD, Pijoan C, Murtaugh MP. Characterization of prototype and clinically defined strains of Streptococcus suis by genomic fingerprinting [J]. Clin Microbiol 1990, 28(11):2462-2466.
66 Devriese L A, Ceyssencs K, Hommez J, et al .Characteristics of different Streptococcus suis ecovars and description of simplified identification[J]. Vet Microbiol, 1991, 26: 141-150.
67 Perch B,Pedersen K B, Henrichsen J. Serology of capsulated streptococci pathogenic for pigs: six new serotypes of Streptococcus suis [J] .Clin Microbiol, 1983, 17(6):993-996.
68 Tikkanen K, Hayrinen J, Pelkonen S. Immunoblot analysis of bacterial polysaccharides: application to the type-specific polysaccharides of Streptococcus suis and Streptococcus agalactiae [J]. Immunol Methods 1995, 1;187(2):233-244
69 I.Soedannanto,F.H.Pasaribu,I.W.T.Wibawan,and C.LAmmler. Identification and Molecular Characterization of Serological Group C Streptococci Isolated from Diseased Pigs and Monkeys in Indonesia
70 Ana I Vela, Joaquin Goyache, Carmen Tarradas . Analysis of genetic diversity of streptococcus suis clinical isolates fron pigs in spain by pulsed-field gel electrophoresis[J] . Clin Microbio , 2003, 41(6):2498-2502.
71 Hampson D J, Trott D J, Clarke IL, et al. Population structure of Australian isolates of Streptococcus suis[J]. J Clin Microbiol. 1993, 31:2895-2900
72 Mwaniki C G, Robertson I D, Trott D J. Clonal analysis and virulence of Australian isolates of Streptococcus suis type 2[J]. Epidemiol Infect, 1994,113:321-334.
73 Smith H E, Rijnsburger M, Stockhofe-Zurwieden, et al. Virulent strains of Streptococcus suis type 2 and highly virulent strains of Streptococcus suis type 1 can be recognized by a unique ribotype profile[J]. J Clin Microbiol, 1997,35:1049-1053
74 Beaudoin M, Harel J ,Higgins R, et al. Molecular analysis of isolates of Streptococcus suis type 2 by restriction-endonuclease digested DNA separated on SDS-PAGE and by hybridization with rRNA probe[J]. J Gen Microbiol, 1992a, 138:2639-2645
75 Staats J J, Plattner B L, Nirtfeld j, et al. Use of ribotyping and hemolysin activity to identify highly virulent Streptococcus suis type 2 isolates[J]. J Clin Microbiol, 1998,36:15-18
76 蔡宝祥．家畜传染病学[M]．北京：中国农业出版社，1998．93
1 陆承平，兽医微生物．第三版．北京：中国农业出版社，2001，209
2 Nicholson M..Ferdinand LL.,Sampson JS.Benin A.Balter S..Pinto SWL.Dowell SF.,Facklam RR,.Carlone GM,and Beall B.Analysis of immunoreactivity to a Streptococcus equi subsp.zooepidemicus M-Iike protein to confirm an outbreak of poststreptococcal glomerulonephritis and sequences of M-like proteins from isolates obtained from different host species.J.Clin.Microbiol.,2000;38:4126-4130
3 Arends J P,Zanen H C.Meningitis caused by Streptococcus suis in human.Rev Infect Dis,1988,10:131-137
4 Stattas J J.Feder I.Okwumabua O,et al.Streptococcus Suis:past and present.Vet Res commun, 1997,21 (6):381 -407.Review
5 Knodler LA,Celli J and Finaly BB.Pathogenic trickery:deception of host cell processes.Nature Rev Mol Cell Biol 2001,2:578-588
6 谢怡敏．整合素系统对人精子顶体反应的作用．四川生理科学杂志，2003，25(1)：29-32．
7 沈建箴，吕连煌．血浆纤连蛋白水平在急性白血病中的变化．中华医院感染学杂志，2000；10
8 Liaw L, Skinner MP, Raines EW, et al.The adhesive and migratory ef fects of osteopontic are mediad via distinct cell surface integrins.J Clin Invest, 1995, 95 (2) :713-724.
9 Hynes RO.Interin:versatility, modulation and signaling in cell adhesion.Cell, 1992, 69 (1) :11-25.
10 Sebag J, Balazs EA.Morphology and ultrastructure of human vitreous fibers.Invest Ophthalmol Vis Sci, 1989, 30:1867-1871.
11 Baekalow FJ, and Schwarzbauer JE. Localization of the major hepair-binding site in fibronectin. J Biol Chem 1991, 266:7812-7812
12 Armstrong PB, Armstrong M T. Intercellular invasion and the organizatoinal stablity of tissues: a role for fibronectin. Biochim. Biophys. Acta.2000,470(2):09
13 Yamamoto Y , Tsutsumi Y , M ayumi T. M olecular design of bioconjugated cell adhesion peptide with a water—soluble polymeric modifier for enhancement of antimetastatic effect. Curr Drug Targets, 2002 ,3(2): 123
14 Ruoslahti E. Fibronectin and ltrs Receptor. Annu. Rev. Biochem , 1988,57:375-413
15 Mostafavi-Pour Z, Askari JA, Whittard JD and Humphries MJ. Identification of a novel heparin-binding site in the alternatively spliced ⅢCS region of fibronectin: roles of integrins and proteoglycans in cell adhesion to fibronectin splice variants. Matrix Biol. 2001, 20:63-73.
16 Hahn L and Yamada K. Identification and isolation of a collagen-binding fragement of the adhesive glycoprotein fibronectin.Proc Natl Acad Sci USA 1979, 76:1160-1163
17 朱肖奇，秦廷武．细胞黏附基础与肌腱组织工程．生物医学工程学杂志，2004，21(2)：329．332
18 Chothia C, Jones EY.The Moleuclar Structure of Cell Adhesion Moleuclars.Annu.Rev. Biochem, 1997,66(8):3
19 Lin H,Lal R.Clegg DO.Imaging and Mapping Heparin-Bind Sites on Single Fibronectin M olecules with Atom ic Force M iroscopy. Biochemistry, 2000,39(3):9
20 Patel RS, Odermatt E, Schwarzbauer JE and Hynes RO. Organization of the fibronectin gene provides evidence for exon shuffling during evolution. EMBO J. 1987, 6: 2565-2572.
1 Collazos J, Echevarria M J, Ayarza R, et al. Streptococcus zooepidemicus septicarthritis :case report and reviewof group C streptococcal arthritis. Clin Infect Dis, 1992,16:744 - 746.
2 Barnham M, Ljunggren A, Mcintyre M. Human infection with Streptococcus zooepidemicus (Lancefield group C) : three case reports. Epidem Infect, 1987,98:183 - 190.
3 Hynes, R. O. 1990. Fibronectins. Springer Verlag, New York.
4 Mosher, D. F. 1989. Fibronectin. Academic Press Inc., San Diego, Calif.
5 Ruoslahti, E. E.G.Hayman, and M. D. Pierschbacher. 1985. Extracellular matrices and cell adhesion. Arteriosclerosis 5:581-594.
6 J 萨姆布鲁克，EF弗里奇，T曼尼阿蒂斯。金冬雁，孟黎枫等译．分子克隆实验指南。第二版．北京：科学出版社，1993
7 Chhatwal GS.Anchorless adhesions and invasions of Gram-positive bacteria:a new class of virulence factors.Trends Microbiol..2002;10:205-208
8 Flock, J.-I., G. Froman, K. Jonsson, B. Guss, C. Signas, B. Nilsson, G.Raucci, M. Hook, T. Wadstrom, and M. Lindberg. 1987. Cloning and expression of the gene for a fibronectin-binding protein from Staphylococcus aureus. EMBO J. 6:2351-2357.
9 Jonsson, K., C. Signas, H.-P. Muller, and M. Lindberg. 1991. Two different genes encode fibronectin binding proteins in Staphylococcus. The complete nucleotide sequence and characterization of the second gene. Eur. J. Biochem. 202:1041-1048.
10 Signas, C, G. Raucci, K. Jonsson, P.-E. Lindgren, G. M. Anantharamaiah.M. Hook, and M. Lindberg. 1989. Nucleotide sequence of the gene for a fibronectin-binding protein from Staphylococcus aureus: use of this peptide sequence in the synthesis of biologically active peptides. Proc. Natl. Acad.Sci. USA 86:699-703.
11 Sela, S., A. Aviv, A. Tovi, 1. Burstein, M. G. Caparon, and E. Hanski. 1993.Protein F: an adhesin of Streptococcus pyogenes binds fibronectin via two distinct domains. Mol. Microbiol. 10:1049-1055.
12 Courtney, H. S., Y. Li, J. B. Dale, and D. L. Hasty. 1994. Cloning, sequencing and expression of a fibronectin/fibrinogen-binding protein from group A streptococci. Infect. Immun. 62:3937-3946.
13 Chen, C. C, and P. P. Cleary. 1990. Complete nucleotide sequence of the streptococcal C5a peptidase gene of Streptococcus pyogenes. J. Biol. Chem.265:3161-3167.
14 Whatmore AM.Streptococcus pyogenes sclB encodes aputative hypervariable surface protein with a collagen-like repetitive structure.Microbiol.,2001;147:419-429.
15 Greeff A,Herma B,Robin V.et al.Contribution of fibronectin-binding protein to pathogenesis of Streptococcus suis Serotype2.1nfect.lmmun.,2002;70:1319-1325.
16 Shigetada K,Eiji E,Yutaka T,et al.Systemic and mucosal immunizations with fibronectin-binding protein FBP54 induce protective immune responses against Streptococcus pyogenes challenge in mice.lnfect.Immun.,2001;69:924-930.
1 Greeff A , Herma B , Robin V , et al. Cont ribution of fibronectin-binding protein to pat hogenesis of Streptococcus suis serotype2[J]. Infect Immun ,2000 ,68 (2) :637-643.
2 Finlay B B , Cossart P. Exploitation of mammalian host cell functions by bacterial pathogens [J]. Science, 1997,276:718-725.
3 Greeff A , Herma B , Robin V , et al. Contribution of fibronectin-binding protein to pathogenesis of Streptococcus suis serotype 2[J]. Infect Immun ,2000,68 (2) :637-643.
4 Joh D,wann ER,Kreikemeyer B,Speziale P,H66k MRole of fibronectin-binding MSCRAMMs in bacterial adherence and entry into mammalian cell.Matrix Biol., 1999; 18:211-223
5 peacock SJ,lina G,Etienne J,and Foster TJ.Staphylococcus schleiferi subsp. Schleiferi expresses a fibronectin-binding protein.Infect.Immun.,1999;67:4272-4275
6 Allignet J.Aubert S,Dyke KGH,and Solh N. Staphylococcus caprae strains carry determinants known to be involved in pathogenicity:a gene encoding an autolysin-binding fibronectin and the ica operon involved in biofilm formation.Infect.Immun.,2001;69:712-718
7 Chia JS.Yeh CY,and Chen JY.Identification of a fibronectin binding protein from Streptococcus mutans. Infect.Immun.2000;68:1864-1870
8 Christie J.McNab R.and Jenkinson HF.Expressin of fibronectin-binding protein FbpA modulates adhesion in Streptococcus gordonii.Microbiol.,2002; 148:1615-1625
9 Latorre M, Alvalez M, Fernandez J M ,et al. A case of meningitis due to Streptococcus zooepidemicus[J]. Clin Infect Dis ,1993 ,17 :932-933.
10 Martinez2Luengas F, Inclan G M, Paster A , et al. Endocarditis due to Streptococcus zooepidemicus[J]. Can Med Assoc J ,1982,127 :13.
11 Collazos J , Echevarria M J , Ayarza R ,et al . Streptococcus zooepidemicus septic arthritis : case report and review of group C streptococcal art hritis[J]. Clin Infect Dis , 1992 , 16 : 744-746.
12 Rose H D, Allen J R ,and Witte G. Streptococcus zooepidemicus (group C) pneumonia in a human [J]. J Clin Microbiol, 1980,11; 76-78.
13 Barham M, Thorton T J, Lange K. Nephritis caused by S treptococcus zooepidemicus (Lancefield group C) [J]. Lancet Ⅰ,1983 ,945-948.
14 Center for disease control. Group C streptococcal infections associated with eating homemade cheese [J]. New Mexico Morbid Mortal Weekly Rep, 1983 ,32 :510-516.
15 陆承平．兽医微生物学(第三版)[M]．北京：中国农业出版社,2001，204-212．
16 姚火春，陈国强，陆承平．猪链球菌1998分离株病原特性鉴定[J]．南京农业大学学报，1999，22 (2)：67—70．
17 刘佩红、沈素芳、于永康，等．上海地区猪源链球菌病原特性鉴定[J]．中国兽医学报．2001．21(1)：42-46．
18 萨姆布鲁克，EF弗里奇，T曼尼阿蒂斯。金冬雁，孟黎枫等译．分子克隆实验指南。第二版．北京：科学出版社，1993
19 Chhatwal GS.Anchorless sdhesins and invasions of Gram-positive bacteria:a new class of virulence factors.Trends Microbiol..2002;10:205-208.
1 Areds,J.P.,and H.C.Zanen.Meningitis caused by Streptococcus suis in humans.Rev.Infect Dis., 1988; 10:131 - 137
2 Chanter,N.,P.W.Jones,and T.J.L.Alexander.Meningitis in pigs caused by Streptococcus suis aspecularive review.Vet.Microbiol., 1993;36:39-55
3 Gottschalk M,&Segura M.The pathogenesis of the meningitis caused by streptococcus suis:the unresolved questions.Vet.Microbiol.,2000;76:259-272
4 Barnham M, Ljunggren A, Mcintyre M. Human infection with Streptococcus zooepidemicus (Lancefield group C) : three case reports. Epidem Infect, 1987,98:183 - 190.
5 范红结，陆承平，唐家琪．马链球菌兽疫亚种类M基因和猪链球菌2型mrp基因片段的融合表达及仔猪免疫试验．南京农业大学学报，2003，26(4)：78-81．
6 Sharp M W, Prince MJ ,Gibbens J. Streptococcus equi subsp, zooepidemicus infection and bovine mastitis. Vet Rec, 1995,137: 128-129.
7 陆承平．兽医微生物学．第三版．北京：中国农业出版社，2001，233-246．
8 Field H I, Buntain D and Done J T.Studies on piglet mortality.Ⅰ. Streptococcal meningitis and arthritis. Vet Rec, 1954,66:453-455
9 Berry A M , Paton J C.Sequence heterogeneity of PsaA , a 37kilodalton putative adhesin essential for virulence of St reptococcus pneumoniae[i]. Infect Immun ,1996 , 64 :5255 - 5262.
10 Janulczyk R, Pallon J , Bjoirck L. Identification and characterization of a St reptococcus pyogenes ABC transporter with multiple specificity for metal cations[J]. Mol Microbiol, 1999 , 34 : 596 -606.
11 Kolenbrander P E , Andersen R N , Baker R A , et al.The adhesion-associated sca operon in Streptococcus gordonii encodes an inducible high-affinity ABC transporter for Mn2 + uptake[J]. J Bacteriol, 1998,180:290-295.
12 Caballero A R, Lottenberg R, Johnston K.Cloning .expressing .sequence analysis , and characterization of Streptokinase secreted by porcine and equine isolates of Streptococcus equisimilis[J]. Infect Immun. 1999 , 67 (12): 6478-6486.
13 Benkirane R, Gottschalk M.Dubreuil J D. Identification of Streptococcus suis 60-kDa heat-shock protein using western blotting[J]. Microbiol Lett, 1997,153(2):379-385.
14 Knodler LA.Celli J and Finaly BB.Pathogenic trickery deception of host cell processes.Nature Rev Mol Cell Biol 2001,2:578-588
15 Greeff A.Herma B.Robin V,et al.Contribution of fibronectin-binding protein to pathogenesis of Streptococcus suis capsular type2.Infect.Immun.,2002;70:1319-1325.
16 Myhre E B , Kuusela P.Binding of human fibronectin to group A ,C , and G streptococci [J]. Infect Immun, 1983, 40:29-34.
17 Walker,J.A.and Timoney, J.F.(1998) Molecular basis of variation in protective SzP proteins of Streptococcus zooepidemicus.Am.J.Vet.Res.59,1129-1133.
1 Hasty D LItzbak ofek,Courtney H S,et al.Multiple adhesions of streptococci.Infect Immun, 1992,60(6):2174-2152
2 Beachey E H,Simpson W A.The adherence of group A streptococci to oropharyn-geal cells:The lipoteichoic acid adhesion and fibronectin receptor. Infection, 1982,10:107-101
3 Tamura GS , Rubens CE . Group B Streptococci(GBS) adhere to a variant of fibronectin attached to a solid phase [J]. Molecular Micobiology 1995,15:581-589.
4 Christie J,McNab R, Jenkinson HE Expression of fibronectin-binding protein FbpA modulates adhesion in streptococcus gordonii [J]. Microbiol. 2002,148:1615-1625.
5 Lindmark H, Jacobsson K,Frykberg L,and Guss B.Fibronectin-Binding Protein of Streptococcus equi subsp.zooepidemicus.Infect.Immun.,l996;64:3993-3999
6 Myhre EB and Kuusela P.Binding of Human Fibronectin to Group A,C and G Streptococci.Infect.Immun., 1983;40:29-34
7 Lindmark H,Jonsson P,Engvall EO and Guss B.Pulsed-field gel electrophoresis and distribution of the genes zag and fnz in isolates of Streptococcus equi.Res.Vet.Sci., 1999;66:93-99.
8 Hynes,R.O. 1990.Fibronectins.SpringerVerlag,NewYork.
9 H.S.Courtney,D.L.Hasty,Y.Li,H.C.Chiang,J.L.Thacker,J.B.Dale,Serum opacity factor is a major fibronectin-binding protein and a virulence determinant of M type2 Streptococcus pyosenes,Mol.Microbiol.32(1999)89-98.
10 Y.Terao,S.Kawabata,M.Nakata,I.Nakagawa,S.Hamada,Molecular characterization of a novel fibronectin-binding protein of Streptococcus pyogenes strains isolated from toxic shock-like syndrome patients,J.Biol.Chem.277(2002)47428-47435.
11 Kyongsu Hong. Identification and characterization of a novel fibronectin-binding protein protein fron Streptococcus equi subspecies zooepidemicus strain VTU211.[J]. Immunology and Medical Microbiology.2005,45:231-237.