河北省猪链球菌病病原学调查与分析
|
摘要
猪链球菌(Streptococcus suis)可引起猪败血症、脑膜炎、心内膜炎和关节炎,也是一种重要的人畜共患病病原,具有重要的公共生学意义。因此,开展猪链球菌病病原学调查与监测,对于该病的防治具有重要的理论和实践意义。本论文研究工作涉及河北省不同地区猪链球菌的血清型监测与分析,致病性猪链球菌的耐药性和毒力基因分析,利用优势致病菌株研制猪链球菌病价灭活疫苗,旨在了解河北省猪链球菌病的流行情况,为猪链球菌病的防治提供科学依据。
从河北省石家庄、邢台、张家口、沧州、唐山、秦皇岛等地采集临床健康猪鼻拭子600份,经增菌分离培养、革兰染色镜检、PCR鉴定猪链球菌种及分离菌株血清型鉴定。结果表明,从600份鼻拭子样品中共检出148株猪链球菌,检出率为24.67%,其中27株为猪链球菌7型,24株为猪链球菌2型,20株为猪链球菌9型,2株为猪链球菌1型,75株未定血清型。由此表明,河北省正常猪群中猪携带的猪链球菌血清型呈现复杂多样的特点。
对2005-2012年从河北省各地区临床病死猪分离获得的96株猪源链球菌进行了生物学特性鉴定及血清分群。结果表明,分离的链球菌以兰氏D群为主,占34.4%,其次为C群(18.8%)。利用PCR扩增猪链球菌的种特异性gdh基因以及荚膜多糖cpslI、cps2J、cps7H和cps9H基因,对96株链球菌分离株进行猪链球菌种的鉴定和分型。结果显示,属于猪链球菌的为47株,其中猪链球菌2型(SS2)为65.96%(31/47),SS7为2.13%(1/47),SS9为4.25%(2/47),其它血清型为27.66%(13/47)。
采用微量稀释法测定了96株猪源链球菌对27种药物的体外最小抑菌浓度(MIC)。结果显示,94.8%的菌株呈现多重耐药,耐药谱型达14种；对磺胺类药物、氨基糖苷类药物、四环素类药物、林可胺类药物、大环内酯类药物的耐药性最为严重,对青霉素类、头孢菌素类、喹诺酮类、酰胺醇类耐药性次之；对头孢菌素类药物——头孢噻呋、头孢唑啉、头孢噻吩的敏感率分别为87.5%、85.4%和83.3%。由此表明,猪链球菌临床分离株对常用药物均产生了一定的耐药性。
应用PCR对血清型明确的34株猪链球菌的6个毒力因子(gdh、cps、ef、sly和orf2)进行了检测。结果显示,31株猪链球菌2型分离株表现为9种毒力因子基因型,以cps2+/gdh+/sly+/ef+/mrp+/orf2+和cps2+/gdh+/sly-/ef+/mrp+/orf2+为主,分别占32.3%和35.5%,提示河北省SS2的主要流行菌株为同时具有6种毒力因子的高致病性菌株和sly基因缺失株；1株SS7的基因型为cps7+/gdh+/sly+/ef-/mrp+/orf2+;2株SS9的基因型分别为cps9+/gdh+/sly+/ef-/mrp+/orf2+和cps9+/gdh+/sly-/ef-/mrp+/orf2+。致病性试验结果发现,具有cps2+/gdh+/sly+/ef+/mrp+/orf2+和cps2+/gdh+/sly-/ef+/mrp+/orf2+基因型的菌株,对猪均具有较强的致病性和致死性,死亡率达100%。
利用毒力强、分别属于C、D两个主要流行血清群的的菌株LN-2和BBD-1,研制出猪链球菌病氢氧化铝二价灭活疫苗。免疫攻毒试验结果表明,疫苗对断奶仔猪、育肥猪均具有较好的安全性,用LN-2和BBD-1菌株攻毒,免疫组可获得完全保护。
Streptococcus suis (SS) is the causative agent which can cause septicemia, meningitis, endocarditis and arthritis in pigs. It is also a zoonostic pathogen with potential significance to public health. Therefore, the etiological investigation on swine streptococusis possesses remarkable theoretical and practical values. This study carried out a serotype survey of SS prevalent in different areas of Hebei Province, and analyzed the drug resistances and virulence genes of SS, and developed bivalent inactivated vaccine of swine streptococcosis using dominant pathogenic strains of SS prevalent in the areas of Hebei province in order to provide scientific basis for the prevention of swine streptococcosis.
An enrichment culture, Gram's staining and microscopy, and PCR was implemented from600samples of nosal swabs collected from clinical healthy pigs in Shijiazhuang, Xingtai, Zhangjiakou, Cangzhou, Tangshan and Qinghuangdao of Hebei province. The results showed that148strains (24.67%) of Streptococcus suis were isolated from the samples, and of them,27strains (18.24%) belonged to serotype7,24strains (16.22%) were serotype2,20strains (13.51%) were serotype9, and2strains belonged to serotype1, and the serotypes of remaining75strains (50.68%) were undetermined, suggesting that there are various complex serotypes of SS in clinical healthy pigs.
Ninety-six isolates of SS from sick or dead pigs during2005to2012were identified by biological characteristics and serum grouping. Among these isolates,34.4%mainly belonged to Group D, and18.8%belonged to Group C. The species and genotypes of96isolates were further identified by PCR amplifying species-specific gdh gene and genes (cpsl I, cps2J, cps7H and cps9H) of capsular polysaccharide of SS. The results indicated that47of96isolates were SS in which65.96%(31/47) belonged to serotype2(SS2),2.13%(1/47) was SS7,4.25%(2/47) was SS9and27.66%(13/47) belonged to other serotypes.
The drug resistance of96isolates to27antibiotics was analyzed in vitro by microdilution. The results revealed that most of isolates exhibited obvious drug resistance to14antimicrobial drugs and94.8%of isolates displayed multi-drug resistance in which resistance to sulfonamides, aminoglycosides, tetracyclines, lincosamides and macrolides were most frequent, and then to penicillins, cephalosporins, quinolones and amphenicols.87.5%,85.4%and83.3%of isolates were susceptible to ceftiofur, cefazolin and cephalothin, respectively, showing that SS isolated from clinical sick or dead pigs are resistant to common antimicrobial drugs to some degree.
Six virulence genes(gdh, cps, mrp, ef, sly and orf2) for34isolates of SS were detected by PCR. It was indicated that31out of34SS had9genotypes in which32.3%(10/31) was positive in cps2+lgdh+lepf+/mrp+/sly+lorf2+and35.5%(11/31) in cps2+gdh+sly-ef+mrp+orf2+, showing that the dominant strains of SS in Hebei province are highly pathogenic strains with six virulence genes and those of sly gene deletion; out of34,1(SS7) was positive in cps7+/gdh+/sly+/ef-/mrp+/orf2+, and2(SS9) were positive to cps9+/gdh+/sly+/ef-/mrp+/orf2+and cps9+/gdh+/sly-/ef-/mrp+/orf2+, respectively. Furthermore, animal trials showed that the strains with genotypes of cps2+/gdh+/sly+/ef+/mrp+/orf2+and cps2+/gdh+/sly-/ef+/mrp+/orf2+had stronger pathogenicity and fatality (100%mortality) for pigs.
Bivalent inactivated vaccine with aluminium hydroxide adjuvant of swine streptococcosis was developed with two highly virulent strains of LN-2and BBD-1belonging to serogroup C and D. Challenge trials for the vaccinated animals indicated that the vaccine was safe for weaning pigs and finishing pigs which could provide complete protection against LN-2and BBD-1.
从河北省石家庄、邢台、张家口、沧州、唐山、秦皇岛等地采集临床健康猪鼻拭子600份,经增菌分离培养、革兰染色镜检、PCR鉴定猪链球菌种及分离菌株血清型鉴定。结果表明,从600份鼻拭子样品中共检出148株猪链球菌,检出率为24.67%,其中27株为猪链球菌7型,24株为猪链球菌2型,20株为猪链球菌9型,2株为猪链球菌1型,75株未定血清型。由此表明,河北省正常猪群中猪携带的猪链球菌血清型呈现复杂多样的特点。
对2005-2012年从河北省各地区临床病死猪分离获得的96株猪源链球菌进行了生物学特性鉴定及血清分群。结果表明,分离的链球菌以兰氏D群为主,占34.4%,其次为C群(18.8%)。利用PCR扩增猪链球菌的种特异性gdh基因以及荚膜多糖cpslI、cps2J、cps7H和cps9H基因,对96株链球菌分离株进行猪链球菌种的鉴定和分型。结果显示,属于猪链球菌的为47株,其中猪链球菌2型(SS2)为65.96%(31/47),SS7为2.13%(1/47),SS9为4.25%(2/47),其它血清型为27.66%(13/47)。
采用微量稀释法测定了96株猪源链球菌对27种药物的体外最小抑菌浓度(MIC)。结果显示,94.8%的菌株呈现多重耐药,耐药谱型达14种；对磺胺类药物、氨基糖苷类药物、四环素类药物、林可胺类药物、大环内酯类药物的耐药性最为严重,对青霉素类、头孢菌素类、喹诺酮类、酰胺醇类耐药性次之；对头孢菌素类药物——头孢噻呋、头孢唑啉、头孢噻吩的敏感率分别为87.5%、85.4%和83.3%。由此表明,猪链球菌临床分离株对常用药物均产生了一定的耐药性。
应用PCR对血清型明确的34株猪链球菌的6个毒力因子(gdh、cps、ef、sly和orf2)进行了检测。结果显示,31株猪链球菌2型分离株表现为9种毒力因子基因型,以cps2+/gdh+/sly+/ef+/mrp+/orf2+和cps2+/gdh+/sly-/ef+/mrp+/orf2+为主,分别占32.3%和35.5%,提示河北省SS2的主要流行菌株为同时具有6种毒力因子的高致病性菌株和sly基因缺失株；1株SS7的基因型为cps7+/gdh+/sly+/ef-/mrp+/orf2+;2株SS9的基因型分别为cps9+/gdh+/sly+/ef-/mrp+/orf2+和cps9+/gdh+/sly-/ef-/mrp+/orf2+。致病性试验结果发现,具有cps2+/gdh+/sly+/ef+/mrp+/orf2+和cps2+/gdh+/sly-/ef+/mrp+/orf2+基因型的菌株,对猪均具有较强的致病性和致死性,死亡率达100%。
利用毒力强、分别属于C、D两个主要流行血清群的的菌株LN-2和BBD-1,研制出猪链球菌病氢氧化铝二价灭活疫苗。免疫攻毒试验结果表明,疫苗对断奶仔猪、育肥猪均具有较好的安全性,用LN-2和BBD-1菌株攻毒,免疫组可获得完全保护。
Streptococcus suis (SS) is the causative agent which can cause septicemia, meningitis, endocarditis and arthritis in pigs. It is also a zoonostic pathogen with potential significance to public health. Therefore, the etiological investigation on swine streptococusis possesses remarkable theoretical and practical values. This study carried out a serotype survey of SS prevalent in different areas of Hebei Province, and analyzed the drug resistances and virulence genes of SS, and developed bivalent inactivated vaccine of swine streptococcosis using dominant pathogenic strains of SS prevalent in the areas of Hebei province in order to provide scientific basis for the prevention of swine streptococcosis.
An enrichment culture, Gram's staining and microscopy, and PCR was implemented from600samples of nosal swabs collected from clinical healthy pigs in Shijiazhuang, Xingtai, Zhangjiakou, Cangzhou, Tangshan and Qinghuangdao of Hebei province. The results showed that148strains (24.67%) of Streptococcus suis were isolated from the samples, and of them,27strains (18.24%) belonged to serotype7,24strains (16.22%) were serotype2,20strains (13.51%) were serotype9, and2strains belonged to serotype1, and the serotypes of remaining75strains (50.68%) were undetermined, suggesting that there are various complex serotypes of SS in clinical healthy pigs.
Ninety-six isolates of SS from sick or dead pigs during2005to2012were identified by biological characteristics and serum grouping. Among these isolates,34.4%mainly belonged to Group D, and18.8%belonged to Group C. The species and genotypes of96isolates were further identified by PCR amplifying species-specific gdh gene and genes (cpsl I, cps2J, cps7H and cps9H) of capsular polysaccharide of SS. The results indicated that47of96isolates were SS in which65.96%(31/47) belonged to serotype2(SS2),2.13%(1/47) was SS7,4.25%(2/47) was SS9and27.66%(13/47) belonged to other serotypes.
The drug resistance of96isolates to27antibiotics was analyzed in vitro by microdilution. The results revealed that most of isolates exhibited obvious drug resistance to14antimicrobial drugs and94.8%of isolates displayed multi-drug resistance in which resistance to sulfonamides, aminoglycosides, tetracyclines, lincosamides and macrolides were most frequent, and then to penicillins, cephalosporins, quinolones and amphenicols.87.5%,85.4%and83.3%of isolates were susceptible to ceftiofur, cefazolin and cephalothin, respectively, showing that SS isolated from clinical sick or dead pigs are resistant to common antimicrobial drugs to some degree.
Six virulence genes(gdh, cps, mrp, ef, sly and orf2) for34isolates of SS were detected by PCR. It was indicated that31out of34SS had9genotypes in which32.3%(10/31) was positive in cps2+lgdh+lepf+/mrp+/sly+lorf2+and35.5%(11/31) in cps2+gdh+sly-ef+mrp+orf2+, showing that the dominant strains of SS in Hebei province are highly pathogenic strains with six virulence genes and those of sly gene deletion; out of34,1(SS7) was positive in cps7+/gdh+/sly+/ef-/mrp+/orf2+, and2(SS9) were positive to cps9+/gdh+/sly+/ef-/mrp+/orf2+and cps9+/gdh+/sly-/ef-/mrp+/orf2+, respectively. Furthermore, animal trials showed that the strains with genotypes of cps2+/gdh+/sly+/ef+/mrp+/orf2+and cps2+/gdh+/sly-/ef+/mrp+/orf2+had stronger pathogenicity and fatality (100%mortality) for pigs.
Bivalent inactivated vaccine with aluminium hydroxide adjuvant of swine streptococcosis was developed with two highly virulent strains of LN-2and BBD-1belonging to serogroup C and D. Challenge trials for the vaccinated animals indicated that the vaccine was safe for weaning pigs and finishing pigs which could provide complete protection against LN-2and BBD-1.
引文
[1]Jansen EJ,Van Dorssen CA.meningoencephalitis bij varkens door streptococcen.Tijdschr Diergeneeskd,1951,76:815-832
[2]Staats J J, Feder 1, Okwumabua O, et al. Streptococcus suis:past and present. Vet Res Commun, 1997,21(6):381-407
[3]Touil F, Higgins R, Nadeau M. Isolation of Streptococcus suis from diseased pigs in Canada. Vet Microbiol,1988,17(2):171-177
[4]Rosenkranz M, Elsner HA, Stiirenburg HJ, et al. Streptococcus suis meningitis and septicemia contracted from a wild boar in Germany. J Neurol,2003,250(7):869-870
[5]Clifton-Hadley F A. Studies of Streptococcus suis type 2 infection in pigs. Vet Res Commun,1984, 8(3):217-227
[6]Poggenborg R, Gaini S, Kjaeldgaard P, et al. Streptococcus suis:meningitis, spondylodiscitis and bacteraemia with a serotype 14 strain. Scand J Infect Dis,2008,40(4):346-349
[7]Barbara E.Straw, Jeffery J Zimmermom, Sylvie D'Allaire,等.猪病学.9版.北京：中国农业大学出版社,2008：877-894
[8]Haleis A, Alfa M, Gottschalk M, et al. Meningitis caused by Streptococcus suis serotype 14, North America. Emerg Infect Dis,2009,15(2):350-352.
[9]Cheng AF, Oo KT, Li EK, et al. Septic arthritis caused by Streptococcus suis serotype 2. J Infect, 1987,14(3):237-241
[10]陈耀春.中国动物疫病志.北京：科技出版社,1993,230～233
[11]何家惠,徐筠遐,侯继波,等.一起Ⅱ型链球菌致猪急性败血症暴发流行.中国人兽共患病杂志,2000,16(1)：109
[12]王广和,杨瑞馥,华春涛,等.一种新的人兽共患病病原菌—血液链球菌.中国人兽共患病杂志,1999,15(5)：204-206
[13]Kennedy KJ, Jadeer AA, Ong CW, et al. Two cases of Streptococcus suis endocarditis in Australian piggery workers. Med J Aust,2008,189(7):413
[14]Zalas-Wiecek P, Michalska A, Grabczewska E, et al. Human meningitis caused by Streptococcus suis. J Med Microbiol,2013,62(3):483-485
[15]Marois C, Le Devendec L, Gottschalk M, et al.Detection and molecular typing of Streptococcus suis in tonsils from live pigs in France. Can J Vet Res,2007,71(1):14-22.
[16]Prieto C, Pena J, Suarez P, et al. Isolation and distribution of Streptococcus suis capsular types from diseased pigs in Spain.Zentralbl Veterinarmed B,1993,40(8):544-548
[17 Dekker N, Bouma A, Daemen I, et al. Effect of spatial separation of pigs on spread of Streptococcus suis serotype 9. PLoS One,2013,8(4):1-7
[18]Heath PJ, Hunt BW, Duff JP, et al. Streptococcus suis serotype 14 as a cause of pig disease in the UK. Vet Rec,1996,139(18):450-451
[19]Tian Y, Aarestrup FM, Lu CP. Characterization of Streptococcus suis serotype 7 isolates from diseased pigs in Denmark. Vet Microbiol,2004,103(1-2):55-62
[20]MacLennan M, Foster G, Dick K, et al. Nielsen B.Streptococcus suis serotypes 7,8 and 14 from diseased pigs in Scotland. Vet Rec,1996,139(17):423-424
[21]Aarestrup FM, Jorsal SE, Jensen NE. Serological characterization and antimicrobial susceptibility of Streptococcus suis isolates from diagnostic samples in Denmark during 1995 and 1996. Vet Microbiol,1998,60(1):59-66
[22]Poggenborg R, Gaini S, Kjaeldgaard P, et al. Streptococcus suis:meningitis, spondylodiscitis and bacteraemia with a serotype 14 strain. Scand J Infect Dis,2008,40(4):346-34
[23]Higgins R, Gottschalk M, Quebec. Distribution of Streptococcus suis capsular types in Canada in 1992. Can Vet J,1993,34(7):442
[24]Kerdsin A, Oishi K, Sripakdee S, et al. Clonal dissemination of human isolates of Streptococcus suis serotype 14 in Thailand. J Med Microbiol,2009,58(Pt 11):1508-1513
[25]Camporese A, Tizianel G, Bruschetta G, et al. Human meningitis caused by Streptococcus suis:the first case report from north-eastern Italy. Infez Med,2007,15(2):111-114
[26]Robertson ID, Blackmore DK, Hampson DJ. A longitudinal study of natural infection of piglets with Streptococcus suis types 1 and 2. Epidemiol Infect.1991,107(1):119-126
[27]Enright MR, Alexander TJ, Clifton-Hadley FA. Role of houseflies (Musca domestica) in the epidemiology of Streptococcus suis type 2. Vet Rec.1987,121(6):132-133
[28]白雪梅,张亚兰,孙娜,等.100株猪链球菌的生化检测及药物敏感性分析.中国人兽共患病学报.2006,22(5)：396-398
[29]Smith HE, wisselink HJ, Stockhofe-Zurwieden N, et al. Virulence markers of Streptococcus suis type 1 and 2. Adv Exp Med Biol,1997,418:651-655
[30]Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, et al. 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, 2000,74(3):237-248
[31]Wisselink HJ, Reek FH, Vecht U, et al. Detection of virulent strains of Streptococcus suis type 2 and highly virulent strains of Streptococcus suis type 1 in tonsillar specimens of pigs by PCR. Vet Microbiol,1999,67(2):143-157
[32]Okwumabua O, O'Connor M, Shull E. A polymerase chain reaction (PCR) assay specific for Streptococcus suis based on the gene encoding the glutamate dehydrogenase. FEMS Microbiol Lett,2003,218(1):79-84
[33]Marois C, Bougeard S, Gottschalk M, et al. Multiplex PCR assay for detection of Streptococcus suis species and serotypes 2 and 1/2 in tonsils of live and dead pigs. J Clin Microbiol,2004,42(7): 3169-3175
[34]倪艳秀,何孔旺,王继春,等.检测猪链球菌2型的溶菌酶释放蛋白(MRP)的PCR方法的建立.中国预防兽医学报，2001,23(1)：20～22
[35]李干武,姚火春,陆承平.在猪链球菌江苏分离株中发现新的orf2独立相关基因.农业生物技术学报,2003,11(3)：295-298
[36]赵冉,孙建和,陆承平.猪链球菌国内分离株毒力因子的分布特征.上海交通大学学报,2006,24(6)：495-498
[37]Segura M, Vadeboncoeur N, Gottschalk M, et al. CD14-dependent and independent cytokine and chemokine production by human THP-1 monocytes stimulated by Streptococcus suis capsular type 2.Clin Exp Immunol.2002,127(2):243-254
[38]A1-Numani D, Segura M, Dore M, et al. Up-regulation of ICAM-1, CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes stimulated by Streptococcus suis serotype 2. Clin Exp Immunol,2003, 133(1):67-77
[39]Benga L, Goethe R, Rohde M, et al. Non-encapsulated strains re veal novel insights in invasion and survival of Streptococcus suis in epithelial cells. Cell Microbiol,2004,6(9):867-881
[40]Charland N, Nizet V, Rubens CE, et al. Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells. Infect Immun,2000,68(2):637-643
[41]Vanier G, Segura M, Friedl P, et al. Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2. Infect Immun,2004,72(3):1441-1449
[42]Vecht U, Wisselink H J, Jellema M L, et al. Identification of two proteins associated with virulence of the Streptococcus suis type2. Infect Immun,1991,59(9):3156-3162
[43]Martinez G, Pestana de Castro AF, Ribeiro Pagnani KJ, et al. Clonal distribution of an atypical MRP+, EF*, and suilysin+phenotype of virulent Streptococcus suis serotype 2 strains in Brazil. Can J Vet Res,2003,67(1):52-55.
[44]G. Martinez, A. F. Pestana de Castro, K. Jordao Ribeiro Pagnani. Clonal distribution of an atypical MRP+, EF*, and suilysin+ phenotype of virulent Streptococcus suis serotype 2 strains in Brazil. Can J Vet Res,2003,67(1):52-55
[45]Gottschalk M, Lebrun A, Wisselink H, et al. Production of virulence-related proteins by Canadian strains of Streptococcus suis capsular type 2. Can J Vet Res,1998,62(1):75-79
[46]王建,刘佩红,沈素芳,等.马链球菌兽Ⅱ种类M蛋白亚单位疫苗小鼠免疫试验.中国兽医学报,2006,26(5)：495-497
[47]http://www.Zgny.com.cn/ifm/tech/2005-9-1/31818.shtml
[48]高云飞,苏亚君,李宝臣,等.猪链球菌活疫苗的研制.中国预防兽医学报,2001,23(3)：228-230
[49]Holt ME, Enright MR, Alexander TJ. Immunisation of pigs with killed cultures of Streptococcus suis type 2. Res Vet Sci,1990,48(1):23-27
[50]Wisselink HJ, Stockhofe-Zurwieden N, Hilgers LA, et al. Assessment of protective efficacy of live and killed vaccines based on a non-encapsulated mutant of Streptococcus suis serotype 2. Vet Microbiol,2002,84(1-2):155-168
[51]Wisselink HJ, Vecht U, Stockhofe-Zurwieden N, et al. Protection of pigs against challenge with virulent Streptococcus suis serotype 2 strains by a muramidase-released protein and extracellular factor. Vet Rec,2001,148(15):473-477
[52]Elliott SD, Clifton-Hadley F, Tai J. Streptococcal infection in young pigs. V. An immunogenic polysaccharide from Streptococcus suis type 2 with particular reference to vaccination against streptococcal meningitis in pigs. J Hyg(Lond),1980,85(2):275-285
[53]李明,何孔旺,陆承平,等.猪链球菌2型MRP与EPF基因串联表达蛋自及其免疫保护作用.中国农业科学,2005,38(6)：50-56
[54]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
[55]胡晓抒,朱凤才,汪华,等.人-猪链球菌感染性综合征研究.中华预防医学杂志,2000,34(3)：150～152
[56]Staats J J, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Vet Res Commun, 1997,21(6):381-407
[57]Touil F, Higgins R, Nadeau M. Isolation of Streptococcus suis from diseased pigs in Canada. Vet Microbiol,1988,17(2):171-177
[58]Torremorell M, Calsamiglia M, Pijoan C. Colonization of sucking pigs by Streptococcus suis with particular reference to pathogenic sereotype 2 strains. Can J Vet Res,1998,62(1):21-26
[59]沈健,孙建中,尤玉民,等.如皋市人_猪链球菌感染综合征预防控制效果分析.数理医药学杂志,2000,13(3)：257-258
[60]杨珍,王楷成,范伟兴,等.表观健康猪群携带猪链球菌情况流行病学调查.中国人兽共患病学报,2009,25(10)：977～979
[61]吕立新,何孔旺,倪艳秀,等.从止常屠宰猪扁桃体中分离到致病性猪链球菌2型.中国人兽共患病学报,2008,24(4)：379～383
[62]罗隆泽,王鑫,崔志刚,等.四川资阳地区健康猪2型猪链球菌分离与分子生物学特征分析. 中国人兽共患病学报,2009,25(9)：842-845.
[63]Smith H E, Veenbergen V, van der Velde J, et al. The cps genes of Streptococcus suis serotypes 1,2, and 9:development of rapid serotype-specific PCR assays. J Clin Microbiol,1999,37(10):3146-3152
[64]王淑杰,雷连成,徐敏,等.东北地区猪群链球菌分离鉴定及流行病学调查分析.中国兽医学报,2009,29(7)：877～881
[65]陆承平,姚火春.猪链球菌病与猪链球菌.科学进步与学科发展(下册).南京：东南大学出版社,1999,339-343
[66]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调查.中国兽医杂志,1999,25(11)：8-10
[67]蔡宝祥.家畜传染病学(第2版).北京：农业出版社,1991,186-190
[68]姚火春,陈国强,陆承平.猪链球菌1998分离株病原特性鉴定.南京农业大学学报,1999,22(2)：67-70
[69]何孔旺,陆承平.猪链球菌2型的致病性与毒力因子.中国兽医科技,2000,30(9)：17～18
[70]陈永林,关孚时.动物病原性链球菌的血清学分群鉴定.中国兽医杂志,1993,19(9)：3-4
[71]B.E.斯特劳,S.D.阿莱尔,W.L.蒙加林,等主编.猪病学(第8版)(赵德明,张中秋,沈建忠主译).北京：中国农业大学出版社,2000,579～589
[72]Hommez J, Devriese LA, Henrichses J, et al. Identification and Characterization of streptococcus suis. Vet Microbiol,1986,11(4):349-355
[73]Torremorell M, Calsamiglia M, Pijoan C. Colonization of sucking pigs by streptococcus suis with paticular reference to pathogenic serotype 2 strains. Can J vet Res,1998,62(1):21-26
[74]Kebede M, Chengappa MM, Stuart JG. Isolation and characterization of temperature-sensitive mutants of Streptococcus suis:efficacy trial of the mutant vaccine in mice. Vet Microbiol,1990, 22(2-3):249-257
[75]Tarradas C, Arenas A, Maldonado A, et al. Identification of streptococcus suis isolated from swine: Proposal for biochemical parameters. J Clin Microbiol,1994,32(2):578-580
[76]Gottschalk M, Higgins R, Boundreau M. Use of polyvalent coagglutination reagents for serotyping of streptococcus suis. J Clin Microbiol,1993,31(8):2192-2194
[77]R.E.布坎南,N.E.吉本斯,等.伯杰细菌鉴定手册.北京：科学出版社,1984,681-697
[78]Clifton-Hadley F A. Streptociccus suis type 2 infection. Br Vet J,1983,139(1):1-5
[79]Arends JP, Zanen HC. Meningitis caused by Streptococcus suis in humans. Rev Infect Dis,1988, 10(1):131-137
[80]王丽平,陆承平,唐家琪.32种抗菌药物对临床分离猪源链球菌的体外抗菌活性.微生物学报,2004,44(6)：794～799
[81]Aarestrup FM, Jorsal SE, Jensen NE. Serological characterization and antimicrobial susceptibility of Streptococcus suis isolates from diagnostic samples in Denmark during 1995 and 1996. Vet Microbiol,1998,60(1):59-66
[82]Martel A, Baele M, Devriese LA, et al. Prevalence and mechanism of resistance against macrolides. and lincosamides in Streptococcus suis isolates. Vet Microbiol,2001,83(3):287-297
[83]Kataoka Y, Yoshida T, Sawada T. A 10-year survey of antimicrobial susceptibility of streptococcus suis isolates from swine in Japan. J Vet Med Sci,2000,62(10):1053-1057
[84]Clinical and Laboratory Standard Institute. Performance standards for antimicrobial susceptibility testing; 19th informational supplement. M100-S19.CLSI,2009
[85]Brown AW, Rankin SC, Platt DJ. Detection and characterisation of integrons in Salmonella enterica serotype enteritidis. FEMS Microbiol Lett,2000,191:145-149
[86]Tribble GD, Parker AC, Smith CJ. Genetic structure and transcriptional analysis of a mobilizeble, antibioticresistance transposon from bacteroides, Plasmid,1999,42(1):1-12
[87]Bass L, Liebert CA, Lee MD, et al. Incidence and characterization of integrons, genetic elements mediating multiple-drug resistance, in avian Escherichia coli. Antimicrob Agents Chemother,1999, 43(12):2925-2929
[88]McDonald LC, Kuehne MJ, Tenover FC, et al.Vancomycin-resistant enterococci outside the health-care setting: prevalence, sources, and public health implications. Emerg Infect Dis,1997, 3(3):311-317
[89]Barbara E.Straw, Jeffery J Zimmermom, Sylvie D'Allaire,等.猪病学(9版).北京：中国农业大学出版社,2008：877-894
[90]路玲玲,李蓉,郑玉珍,等.2型猪链球菌毒力因子研究进展.中国卫生检疫杂志,2008,18(3)：570-572
[91]Norton PM, Rolph C, Ward PN, et al. Epithelial invasion and cell lysis by virulent strains of Streptococcus suis is enhanced by the presence of suilysin. FEMS Immunol Med Microbiol,1999, 26 (1):25-35
[92]欧瑜,陆承平.猪链球菌2型国内分离株毒力相关蛋白的分析.微生物学报,2002,42(1)：105-108
[93]曾巧英,陆承平.猪链球菌2型溶菌酶释放蛋白诱导上皮细胞融合和凋亡.微生物学报,2003,43(3)：407-411
[94]Segers RP, Kenter T, de Haan LA, et al. Characterisation of the gene encoding suilysin from Streptococcus suis and expression in field strains. FEMS Microbiol Lett,1998,167(2):255-261
[95]Staats JJ, Plattner BL, Stewart GC, et al. Present of the streptococcus suis suilysin gene and expression of MRP and EF correlates with high virylence in streptococcus suis type 2 isolates. Vet Microbiol,1999,70 (3-4):201-211
[96]Smith HE, Damman M, van der Velde J, 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,1999,67(4):1750-1756
[97]王健.猪链球菌病疫苗的研制：[硕十学位论文].南京：南京农业大学,2001
[98]姜平.兽医生物制品学(第2版).北京：中国农业出版社,2003年,200-203
[99]中华人l民共和国农业部.兽用生物制品质量标准汇编.2006,163-164.
[100]姜天童,徐涤平,刘泽文,等.猪链球菌病多价灭活疫苗安全性和免疫原性试验.中国兽医杂志,2001,(8)：21～22
[101]杜雅楠,胡亚澜,杨莲茹,等.猪链球菌的分离及油乳剂灭活疫苗的研究.中国动物检疫,2001,18(8)：27～28
[102]余玲娜,黄捷,司徒剑谋,等.猪链球菌病C、D、E三价灭活蜂胶疫苗的研制.广东畜牧兽医科技,2012,37(1)：35-38
[103]陈斌,张东,余勇,等.四川省部分猪场猪链球菌病免疫前后的病原及抗体调查.畜牧与兽医,2011,43(11)：57～59
[104]吕宗德,李双福.猪链球菌病疫苗免疫效果跟踪试验.河南畜牧兽医,2011,32(1)：4-5
[2]Staats J J, Feder 1, Okwumabua O, et al. Streptococcus suis:past and present. Vet Res Commun, 1997,21(6):381-407
[3]Touil F, Higgins R, Nadeau M. Isolation of Streptococcus suis from diseased pigs in Canada. Vet Microbiol,1988,17(2):171-177
[4]Rosenkranz M, Elsner HA, Stiirenburg HJ, et al. Streptococcus suis meningitis and septicemia contracted from a wild boar in Germany. J Neurol,2003,250(7):869-870
[5]Clifton-Hadley F A. Studies of Streptococcus suis type 2 infection in pigs. Vet Res Commun,1984, 8(3):217-227
[6]Poggenborg R, Gaini S, Kjaeldgaard P, et al. Streptococcus suis:meningitis, spondylodiscitis and bacteraemia with a serotype 14 strain. Scand J Infect Dis,2008,40(4):346-349
[7]Barbara E.Straw, Jeffery J Zimmermom, Sylvie D'Allaire,等.猪病学.9版.北京：中国农业大学出版社,2008：877-894
[8]Haleis A, Alfa M, Gottschalk M, et al. Meningitis caused by Streptococcus suis serotype 14, North America. Emerg Infect Dis,2009,15(2):350-352.
[9]Cheng AF, Oo KT, Li EK, et al. Septic arthritis caused by Streptococcus suis serotype 2. J Infect, 1987,14(3):237-241
[10]陈耀春.中国动物疫病志.北京：科技出版社,1993,230～233
[11]何家惠,徐筠遐,侯继波,等.一起Ⅱ型链球菌致猪急性败血症暴发流行.中国人兽共患病杂志,2000,16(1)：109
[12]王广和,杨瑞馥,华春涛,等.一种新的人兽共患病病原菌—血液链球菌.中国人兽共患病杂志,1999,15(5)：204-206
[13]Kennedy KJ, Jadeer AA, Ong CW, et al. Two cases of Streptococcus suis endocarditis in Australian piggery workers. Med J Aust,2008,189(7):413
[14]Zalas-Wiecek P, Michalska A, Grabczewska E, et al. Human meningitis caused by Streptococcus suis. J Med Microbiol,2013,62(3):483-485
[15]Marois C, Le Devendec L, Gottschalk M, et al.Detection and molecular typing of Streptococcus suis in tonsils from live pigs in France. Can J Vet Res,2007,71(1):14-22.
[16]Prieto C, Pena J, Suarez P, et al. Isolation and distribution of Streptococcus suis capsular types from diseased pigs in Spain.Zentralbl Veterinarmed B,1993,40(8):544-548
[17 Dekker N, Bouma A, Daemen I, et al. Effect of spatial separation of pigs on spread of Streptococcus suis serotype 9. PLoS One,2013,8(4):1-7
[18]Heath PJ, Hunt BW, Duff JP, et al. Streptococcus suis serotype 14 as a cause of pig disease in the UK. Vet Rec,1996,139(18):450-451
[19]Tian Y, Aarestrup FM, Lu CP. Characterization of Streptococcus suis serotype 7 isolates from diseased pigs in Denmark. Vet Microbiol,2004,103(1-2):55-62
[20]MacLennan M, Foster G, Dick K, et al. Nielsen B.Streptococcus suis serotypes 7,8 and 14 from diseased pigs in Scotland. Vet Rec,1996,139(17):423-424
[21]Aarestrup FM, Jorsal SE, Jensen NE. Serological characterization and antimicrobial susceptibility of Streptococcus suis isolates from diagnostic samples in Denmark during 1995 and 1996. Vet Microbiol,1998,60(1):59-66
[22]Poggenborg R, Gaini S, Kjaeldgaard P, et al. Streptococcus suis:meningitis, spondylodiscitis and bacteraemia with a serotype 14 strain. Scand J Infect Dis,2008,40(4):346-34
[23]Higgins R, Gottschalk M, Quebec. Distribution of Streptococcus suis capsular types in Canada in 1992. Can Vet J,1993,34(7):442
[24]Kerdsin A, Oishi K, Sripakdee S, et al. Clonal dissemination of human isolates of Streptococcus suis serotype 14 in Thailand. J Med Microbiol,2009,58(Pt 11):1508-1513
[25]Camporese A, Tizianel G, Bruschetta G, et al. Human meningitis caused by Streptococcus suis:the first case report from north-eastern Italy. Infez Med,2007,15(2):111-114
[26]Robertson ID, Blackmore DK, Hampson DJ. A longitudinal study of natural infection of piglets with Streptococcus suis types 1 and 2. Epidemiol Infect.1991,107(1):119-126
[27]Enright MR, Alexander TJ, Clifton-Hadley FA. Role of houseflies (Musca domestica) in the epidemiology of Streptococcus suis type 2. Vet Rec.1987,121(6):132-133
[28]白雪梅,张亚兰,孙娜,等.100株猪链球菌的生化检测及药物敏感性分析.中国人兽共患病学报.2006,22(5)：396-398
[29]Smith HE, wisselink HJ, Stockhofe-Zurwieden N, et al. Virulence markers of Streptococcus suis type 1 and 2. Adv Exp Med Biol,1997,418:651-655
[30]Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, et al. 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, 2000,74(3):237-248
[31]Wisselink HJ, Reek FH, Vecht U, et al. Detection of virulent strains of Streptococcus suis type 2 and highly virulent strains of Streptococcus suis type 1 in tonsillar specimens of pigs by PCR. Vet Microbiol,1999,67(2):143-157
[32]Okwumabua O, O'Connor M, Shull E. A polymerase chain reaction (PCR) assay specific for Streptococcus suis based on the gene encoding the glutamate dehydrogenase. FEMS Microbiol Lett,2003,218(1):79-84
[33]Marois C, Bougeard S, Gottschalk M, et al. Multiplex PCR assay for detection of Streptococcus suis species and serotypes 2 and 1/2 in tonsils of live and dead pigs. J Clin Microbiol,2004,42(7): 3169-3175
[34]倪艳秀,何孔旺,王继春,等.检测猪链球菌2型的溶菌酶释放蛋白(MRP)的PCR方法的建立.中国预防兽医学报，2001,23(1)：20～22
[35]李干武,姚火春,陆承平.在猪链球菌江苏分离株中发现新的orf2独立相关基因.农业生物技术学报,2003,11(3)：295-298
[36]赵冉,孙建和,陆承平.猪链球菌国内分离株毒力因子的分布特征.上海交通大学学报,2006,24(6)：495-498
[37]Segura M, Vadeboncoeur N, Gottschalk M, et al. CD14-dependent and independent cytokine and chemokine production by human THP-1 monocytes stimulated by Streptococcus suis capsular type 2.Clin Exp Immunol.2002,127(2):243-254
[38]A1-Numani D, Segura M, Dore M, et al. Up-regulation of ICAM-1, CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes stimulated by Streptococcus suis serotype 2. Clin Exp Immunol,2003, 133(1):67-77
[39]Benga L, Goethe R, Rohde M, et al. Non-encapsulated strains re veal novel insights in invasion and survival of Streptococcus suis in epithelial cells. Cell Microbiol,2004,6(9):867-881
[40]Charland N, Nizet V, Rubens CE, et al. Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells. Infect Immun,2000,68(2):637-643
[41]Vanier G, Segura M, Friedl P, et al. Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2. Infect Immun,2004,72(3):1441-1449
[42]Vecht U, Wisselink H J, Jellema M L, et al. Identification of two proteins associated with virulence of the Streptococcus suis type2. Infect Immun,1991,59(9):3156-3162
[43]Martinez G, Pestana de Castro AF, Ribeiro Pagnani KJ, et al. Clonal distribution of an atypical MRP+, EF*, and suilysin+phenotype of virulent Streptococcus suis serotype 2 strains in Brazil. Can J Vet Res,2003,67(1):52-55.
[44]G. Martinez, A. F. Pestana de Castro, K. Jordao Ribeiro Pagnani. Clonal distribution of an atypical MRP+, EF*, and suilysin+ phenotype of virulent Streptococcus suis serotype 2 strains in Brazil. Can J Vet Res,2003,67(1):52-55
[45]Gottschalk M, Lebrun A, Wisselink H, et al. Production of virulence-related proteins by Canadian strains of Streptococcus suis capsular type 2. Can J Vet Res,1998,62(1):75-79
[46]王建,刘佩红,沈素芳,等.马链球菌兽Ⅱ种类M蛋白亚单位疫苗小鼠免疫试验.中国兽医学报,2006,26(5)：495-497
[47]http://www.Zgny.com.cn/ifm/tech/2005-9-1/31818.shtml
[48]高云飞,苏亚君,李宝臣,等.猪链球菌活疫苗的研制.中国预防兽医学报,2001,23(3)：228-230
[49]Holt ME, Enright MR, Alexander TJ. Immunisation of pigs with killed cultures of Streptococcus suis type 2. Res Vet Sci,1990,48(1):23-27
[50]Wisselink HJ, Stockhofe-Zurwieden N, Hilgers LA, et al. Assessment of protective efficacy of live and killed vaccines based on a non-encapsulated mutant of Streptococcus suis serotype 2. Vet Microbiol,2002,84(1-2):155-168
[51]Wisselink HJ, Vecht U, Stockhofe-Zurwieden N, et al. Protection of pigs against challenge with virulent Streptococcus suis serotype 2 strains by a muramidase-released protein and extracellular factor. Vet Rec,2001,148(15):473-477
[52]Elliott SD, Clifton-Hadley F, Tai J. Streptococcal infection in young pigs. V. An immunogenic polysaccharide from Streptococcus suis type 2 with particular reference to vaccination against streptococcal meningitis in pigs. J Hyg(Lond),1980,85(2):275-285
[53]李明,何孔旺,陆承平,等.猪链球菌2型MRP与EPF基因串联表达蛋自及其免疫保护作用.中国农业科学,2005,38(6)：50-56
[54]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
[55]胡晓抒,朱凤才,汪华,等.人-猪链球菌感染性综合征研究.中华预防医学杂志,2000,34(3)：150～152
[56]Staats J J, Feder I, Okwumabua O, et al. Streptococcus suis:past and present. Vet Res Commun, 1997,21(6):381-407
[57]Touil F, Higgins R, Nadeau M. Isolation of Streptococcus suis from diseased pigs in Canada. Vet Microbiol,1988,17(2):171-177
[58]Torremorell M, Calsamiglia M, Pijoan C. Colonization of sucking pigs by Streptococcus suis with particular reference to pathogenic sereotype 2 strains. Can J Vet Res,1998,62(1):21-26
[59]沈健,孙建中,尤玉民,等.如皋市人_猪链球菌感染综合征预防控制效果分析.数理医药学杂志,2000,13(3)：257-258
[60]杨珍,王楷成,范伟兴,等.表观健康猪群携带猪链球菌情况流行病学调查.中国人兽共患病学报,2009,25(10)：977～979
[61]吕立新,何孔旺,倪艳秀,等.从止常屠宰猪扁桃体中分离到致病性猪链球菌2型.中国人兽共患病学报,2008,24(4)：379～383
[62]罗隆泽,王鑫,崔志刚,等.四川资阳地区健康猪2型猪链球菌分离与分子生物学特征分析. 中国人兽共患病学报,2009,25(9)：842-845.
[63]Smith H E, Veenbergen V, van der Velde J, et al. The cps genes of Streptococcus suis serotypes 1,2, and 9:development of rapid serotype-specific PCR assays. J Clin Microbiol,1999,37(10):3146-3152
[64]王淑杰,雷连成,徐敏,等.东北地区猪群链球菌分离鉴定及流行病学调查分析.中国兽医学报,2009,29(7)：877～881
[65]陆承平,姚火春.猪链球菌病与猪链球菌.科学进步与学科发展(下册).南京：东南大学出版社,1999,339-343
[66]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调查.中国兽医杂志,1999,25(11)：8-10
[67]蔡宝祥.家畜传染病学(第2版).北京：农业出版社,1991,186-190
[68]姚火春,陈国强,陆承平.猪链球菌1998分离株病原特性鉴定.南京农业大学学报,1999,22(2)：67-70
[69]何孔旺,陆承平.猪链球菌2型的致病性与毒力因子.中国兽医科技,2000,30(9)：17～18
[70]陈永林,关孚时.动物病原性链球菌的血清学分群鉴定.中国兽医杂志,1993,19(9)：3-4
[71]B.E.斯特劳,S.D.阿莱尔,W.L.蒙加林,等主编.猪病学(第8版)(赵德明,张中秋,沈建忠主译).北京：中国农业大学出版社,2000,579～589
[72]Hommez J, Devriese LA, Henrichses J, et al. Identification and Characterization of streptococcus suis. Vet Microbiol,1986,11(4):349-355
[73]Torremorell M, Calsamiglia M, Pijoan C. Colonization of sucking pigs by streptococcus suis with paticular reference to pathogenic serotype 2 strains. Can J vet Res,1998,62(1):21-26
[74]Kebede M, Chengappa MM, Stuart JG. Isolation and characterization of temperature-sensitive mutants of Streptococcus suis:efficacy trial of the mutant vaccine in mice. Vet Microbiol,1990, 22(2-3):249-257
[75]Tarradas C, Arenas A, Maldonado A, et al. Identification of streptococcus suis isolated from swine: Proposal for biochemical parameters. J Clin Microbiol,1994,32(2):578-580
[76]Gottschalk M, Higgins R, Boundreau M. Use of polyvalent coagglutination reagents for serotyping of streptococcus suis. J Clin Microbiol,1993,31(8):2192-2194
[77]R.E.布坎南,N.E.吉本斯,等.伯杰细菌鉴定手册.北京：科学出版社,1984,681-697
[78]Clifton-Hadley F A. Streptociccus suis type 2 infection. Br Vet J,1983,139(1):1-5
[79]Arends JP, Zanen HC. Meningitis caused by Streptococcus suis in humans. Rev Infect Dis,1988, 10(1):131-137
[80]王丽平,陆承平,唐家琪.32种抗菌药物对临床分离猪源链球菌的体外抗菌活性.微生物学报,2004,44(6)：794～799
[81]Aarestrup FM, Jorsal SE, Jensen NE. Serological characterization and antimicrobial susceptibility of Streptococcus suis isolates from diagnostic samples in Denmark during 1995 and 1996. Vet Microbiol,1998,60(1):59-66
[82]Martel A, Baele M, Devriese LA, et al. Prevalence and mechanism of resistance against macrolides. and lincosamides in Streptococcus suis isolates. Vet Microbiol,2001,83(3):287-297
[83]Kataoka Y, Yoshida T, Sawada T. A 10-year survey of antimicrobial susceptibility of streptococcus suis isolates from swine in Japan. J Vet Med Sci,2000,62(10):1053-1057
[84]Clinical and Laboratory Standard Institute. Performance standards for antimicrobial susceptibility testing; 19th informational supplement. M100-S19.CLSI,2009
[85]Brown AW, Rankin SC, Platt DJ. Detection and characterisation of integrons in Salmonella enterica serotype enteritidis. FEMS Microbiol Lett,2000,191:145-149
[86]Tribble GD, Parker AC, Smith CJ. Genetic structure and transcriptional analysis of a mobilizeble, antibioticresistance transposon from bacteroides, Plasmid,1999,42(1):1-12
[87]Bass L, Liebert CA, Lee MD, et al. Incidence and characterization of integrons, genetic elements mediating multiple-drug resistance, in avian Escherichia coli. Antimicrob Agents Chemother,1999, 43(12):2925-2929
[88]McDonald LC, Kuehne MJ, Tenover FC, et al.Vancomycin-resistant enterococci outside the health-care setting: prevalence, sources, and public health implications. Emerg Infect Dis,1997, 3(3):311-317
[89]Barbara E.Straw, Jeffery J Zimmermom, Sylvie D'Allaire,等.猪病学(9版).北京：中国农业大学出版社,2008：877-894
[90]路玲玲,李蓉,郑玉珍,等.2型猪链球菌毒力因子研究进展.中国卫生检疫杂志,2008,18(3)：570-572
[91]Norton PM, Rolph C, Ward PN, et al. Epithelial invasion and cell lysis by virulent strains of Streptococcus suis is enhanced by the presence of suilysin. FEMS Immunol Med Microbiol,1999, 26 (1):25-35
[92]欧瑜,陆承平.猪链球菌2型国内分离株毒力相关蛋白的分析.微生物学报,2002,42(1)：105-108
[93]曾巧英,陆承平.猪链球菌2型溶菌酶释放蛋白诱导上皮细胞融合和凋亡.微生物学报,2003,43(3)：407-411
[94]Segers RP, Kenter T, de Haan LA, et al. Characterisation of the gene encoding suilysin from Streptococcus suis and expression in field strains. FEMS Microbiol Lett,1998,167(2):255-261
[95]Staats JJ, Plattner BL, Stewart GC, et al. Present of the streptococcus suis suilysin gene and expression of MRP and EF correlates with high virylence in streptococcus suis type 2 isolates. Vet Microbiol,1999,70 (3-4):201-211
[96]Smith HE, Damman M, van der Velde J, 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,1999,67(4):1750-1756
[97]王健.猪链球菌病疫苗的研制：[硕十学位论文].南京：南京农业大学,2001
[98]姜平.兽医生物制品学(第2版).北京：中国农业出版社,2003年,200-203
[99]中华人l民共和国农业部.兽用生物制品质量标准汇编.2006,163-164.
[100]姜天童,徐涤平,刘泽文,等.猪链球菌病多价灭活疫苗安全性和免疫原性试验.中国兽医杂志,2001,(8)：21～22
[101]杜雅楠,胡亚澜,杨莲茹,等.猪链球菌的分离及油乳剂灭活疫苗的研究.中国动物检疫,2001,18(8)：27～28
[102]余玲娜,黄捷,司徒剑谋,等.猪链球菌病C、D、E三价灭活蜂胶疫苗的研制.广东畜牧兽医科技,2012,37(1)：35-38
[103]陈斌,张东,余勇,等.四川省部分猪场猪链球菌病免疫前后的病原及抗体调查.畜牧与兽医,2011,43(11)：57～59
[104]吕宗德,李双福.猪链球菌病疫苗免疫效果跟踪试验.河南畜牧兽医,2011,32(1)：4-5