猪链球菌（Streptococcus suis）是猪的重要致病菌，同时也是人畜共患病原菌，可导致猪的脑膜炎、败血症等，对全世界的养猪业造成巨大的经济损失。该菌致病血清型众多且复杂，而且同一种血清型菌株之间毒力可能存在较大差异。当前关注较多的是血清2型，对其它致病血清型如血清7型等的种群结构、致病和耐药特征的研究相对较少。该菌可在健康猪扁桃体长期定殖，且同一扁桃体可能存在多种致病血清型,是潜在的传染源。本研究通过采集江苏和浙江地区屠宰场表观健康猪扁桃体、分离猪链球菌并明确其血清型，比较分析不同地区屠宰场猪链球菌流行病学特征；并对从表观健康猪和发病猪分离的22株猪链球菌血清7型菌株进行全基因组测序、药敏试验、斑马鱼毒力试验等，结合NCBI来源的51株血清7型菌株进行多位点序列分型（MLST）、最小核心基因组分型（MCG）分析，研究结果不仅有助于了解江浙地区猪链球菌的发病规律和制定猪链球菌病的防控策略，也为深入理解猪链球菌7型的种群结构、致病和耐药提供参考，加深对猪链球菌的病原特性认识。
1. 江浙地区屠宰场猪链球菌流行病学调查
2020年于江苏某市屠宰场采集表观健康猪扁桃体64份，猪链球菌阳性样本为35份，阳性率为54.68%，分离到血清16型、4型、7型、31型、9型、3型、5型等36株猪链球菌；2020年在浙江某市屠宰场采集表观健康猪扁桃体70份，猪链球菌阳性的扁桃体为46份，阳性率为65.71%，分离到血清16型、3型、31型、8型、2型、9型等42株猪链球菌。比较分析发现：江浙地区屠宰场生猪携带猪链球菌的阳性率均超过50%；猪链球菌2型在江苏地区并未检出，在浙江地区的分离率也仅为7.14%；血清16型在两个地区的分离率均最高，值得关注。同时，结合本课题组前期在江苏地区采集的样品，2017-2020年从该地区采集表观健康猪扁桃体和鼻拭子样本518份，阳性样本为346份（66.79%），共分离到441株猪链球菌，采用PCR的方法进一步分型鉴定，发现传统血清型有371株（84.12%），新荚膜基因簇（NCL）菌株有21株（4.76%），未定型的菌株有49株（11.11%）；传统血清型中31型分离率最高，占13.6%（60/441），其次是9型（11.33%）、16型（10.88%）、2型（7.48%）、4型（7%）、3型（6.8%）、7型（4.98%）等；新荚膜基因簇（NCL）菌株中，分离率最高的为NCL1和NCL4型，各占28.57%（6/25）。在83份扁桃体样品中（16%）中检出2种及以上不同血清型，其中一份扁桃体分离出5种不同血清型。
2. 猪链球菌血清7型病原与耐药特征
血清7型是猪链球菌主要致病血清型之一，但目前对其种群结构、病原和耐药特性了解十分有限。本研究对从表观健康猪和发病猪分离的22株猪链球菌7型菌株进行全基因组测序，同时结合NCBI来源的51株血清7型全基因组序列进行MCG分型，发现猪链球菌血清7型菌株主要分为4个MCG群，即MCG1、MCG3、MCG4、MCG7-2。通过MLST分型发现猪链球菌血清7型菌株主要分为ST373型、ST94型、ST225型、ST29型、ST1611型和ST1612型，其中ST1611和ST1612是首次发现的ST型；ST373型菌株均属于MCG1群，ST29型和ST225型均属于MCG4群；本实验室来源的22株血清7型菌株ST型主要集中于ST373、ST225和ST29。使用11大类25种抗生素对本实验室来源的22株血清7型菌株进行耐药性试验并检测耐药基因：根据多重耐药菌株的判定标准，对3类及以上抗生素耐药的有16株，占比72.72%；72.7%（16/22）和18.18%（4/22）菌株分别有四环素类耐药基因tet(O)和tet(M)，相应地86.36%（19/22）的菌株对四环素类抗生素耐药，除了3株菌WUSS413、WUSS415和WUSS417之外，其余菌株耐药基因与表型均相符；77.27%（17/22）的菌株分布大环内酯类和林可酰胺类耐药基因erm(B)，药敏试验结果表明，86.3%（19/22）的菌株对大环内酯类抗生素耐药，86.3%（19/22）的菌株对林可酰胺类抗生素耐药，除WUSS366和WUSS413无耐药基因分布但却有耐药表型外，其余菌株耐药基因与表型相符；22.72%（5/22）的菌株分布氨基糖苷类耐药基因ant(6)-Ia和aac(6’) -aph(2’’)，药敏试验结果表明，18.18%（4/22）的菌株对氨基糖苷类抗生素耐药，除WUSS415分布有耐药基因但无耐药表型外，其余菌株耐药基因与表型相符。血清7型菌株对β-内酰胺类、利福霉素类、糖肽类、恶唑烷酮类、喹诺酮类、酰胺醇类、截短侧耳素类抗生素均敏感。毒力基因分析发现，ST373型菌株的溶血素基因sly都是无义突变，而ST29型菌株均是sly-。选择6株代表菌株进行了溶血活性试验，发现WUSS401（ST373、sly无义突变）、WUSS013（ST255、sly+）有溶血活性，WUSS417（ST1611、sly+）、WUSS415（ST1611、sly+）、WUSS413（ST29、sly-）、2018WUSS101（ST1612、sly-）无溶血活性；WUSS417和WUSS415携带sly基因但与溶血表型不符，可能原因是该基因不表达或水平比较低；WUSS401菌株sly无义突变却有溶血活性，这可能该菌株存在其它溶血因子。通过斑马鱼毒力试验，发现3株WUSS401、WUSS417、WUSS013对斑马鱼的致死率为86.6-93.3%。

Streptococcus suis is an important pathogen of pigs and also a zoonotic pathogen. It can cause meningitis and sepsis in pigs and huge economic losses to the pig industry worldwide. The pathogenic serotypes of this bacterium are numerous and complex, and there may be large differences in virulence between strains of the same serotype. Currently, more attention is paid to serotype 2, and there are relatively few studies on the population structure, pathogenicity and antimicrobial resistance of other pathogenic serotypes, such as serotype 7. The bacterium can colonize the tonsils of healthy pigs for a long time, and there may be multiple pathogenic serotypes in the same tonsil, which is a potential source of infection. In this study, S. suis strains were isolated and serotyped from tonsils from pigs in slaughterhouses in Jiangsu and Zhejiang provinces, and the epidemiological characteristics of S. suis in these two regions were analyzed and compared. In addition, 22 S. suis serotype 7 strains isolated from healthy and diseased pigs were subjected to whole genome sequencing, antimicrobial sensitivity test, and zebrafish virulence test; the multilocus sequence typing (MLST) and minimum core genotyping (MCG) analyses were performed for these serotype 7 strains together with 51 serotype 7 strains whose information was accessed from NCBI. The findings not only help to formulate prevention and control strategies for the disease caused by S. suis, but also contribute to the understanding of the population structure, pathogenicity and antimicrobial resistance of S.suis serotype 7.
1. Epidemiological investigation of S. suis in slaughterhouses in Jiangsu and Zhejiang Provinces
In 2020, 64 tonsils from healthy pigs were collected from slaughterhouse in Jiangsu province, of which 35 were S. suis positive (54.68%). In total, 36 strains were isolated, including serotypes 16, 4, 7, 31, 9, 3, and 5. In 2020, 70 tonsils from healthy pigs were collected from slaughterhouse in Zhejiang province, of which 46 were S. suis positive (65.71%). In total, 42 strains were isolated including serotypes 16, 3, 31, 8, 2, and 9. The positive rate of S. suis in the slaughterhouses from Jiangsu and Zhejiang provinces exceeded 50%; S. suis serotype 2 has not been detected in Jiangsu province and the isolation rate of this serotype in Zhejiang is only 7.14%; serotype 16 had the highest isolation rate in both Jiangsu and Zhejiang provinces. Together with the samples isolated in 2017 and 2019 from slaughterhouses in Jiangsu province from our previous studies, 518 samples were collected in total and 346 samples were S. suis positive (66.79%) in Jiangsu province. From 2017 to 2020, a total of 441 S. suis strains were isolated and further serotyped by PCR. There were 371 (84.12%) traditional serotypes, 21 (4.76%) NCL strains, and 49 strains (11.11%) that were non-typeable. It was found that serotype 31 was the highest, accounting for 13.6% (60/441). The remaining strains were serotype 9 (11.33%), serotype 16 (10.88%), serotype 2 (7.48%), serotype 4 (7%), serotype 3 (6.8%), and serotype 7 (4.98%). Among NCL strains the highest isolation rate was NCL1 and NCL4, each accounting for 28.57% (6/25). Two or more serotypes of S. suis were detected in 83 tonsil samples (16%), and one sample even contained five different serotypes strains.
2.  Pathogenicity and antimicrobial resistance of S. suis serotype 7
     S. suis serotype 7 is one of pathogenic serotypes, but the information of its population structure, pathogenicity, and antimicrobial resistance is very limited. 22 strains of S. suis serotype 7 isolated from healthy and diseased pigs were subjected to whole genome sequencing, and a minimum core genome sequence typing (MCG) analysis was performed together with the 51 genome sequences of serotype 7 from NCBI database. We found that S. suis serotype 7 strains are mainly divided into 4 MCG groups, namely MCG1, MCG3, MCG4, and MCG7-2. Multilocus sequence typing (MLST) analysis revealed that S. suis serotype 7 strains are mainly divided into ST373, ST94, ST225, ST29, ST1611, and ST1612, and ST1611 and ST1612 are the new ST types. ST373 strains belong to the MCG1 group, and ST29 and ST225 belong to the MCG4 group; serotype 7 strains from our laboratory were mainly located at ST373, ST225, and ST29. 16 strains were resistant to three or more classes of antimicrobial agents, accounting for 72.72%. 72.7% (16/22) and 18.18% (4/22) of strains contained tet(O) and tet(M) respectively; the antimicrobial susceptibility testing results showed, except for strains WUSS413, WUSS415, and WUSS417, for the rest strains the phenotype of resistance to tetracycline corresponded to the genotype. The macrolides-lincosamides-streptogramin B resistance genes erm(B) (77.27%, 17/22) is present and corresponded to phenotypes of resistance to macrolide antimicrobials tested, with the exception of strains WUSS366 and WUSS413. The aminoglycoside resistance genes ant(6)-Ia (22.72%, 5/22) and aac(6’) -aph(2’’) (9.09%， 2/22) are present alone or in combination and corresponded to phenotypes of resistance to aminoglycoside antimicrobials tested, with the exception of strain WUSS415. All serotype 7 strains from our lab were sensitive to β-lactams, rifamycins, glycopeptides, oxazolidinones, quinolones, amide alcohols, and pleuromutilin antimicrobials tested. Virulence-associated genes analysis found that the hemolysin gene sly of ST373 strains contains nonsense mutation, and all ST29 strains are without sly. Six strains were selected for haemolytic activity testing. We found that: strains WUSS401 (ST373, sly nonsense mutation) and WUSS013 (ST255 sly+) had hemolytic activity; strains WUSS417 (ST1611 sly+), WUSS415 (ST1611 sly+), WUSS413 (ST29 sly-), and 2018WUSS101 (ST1612 sly-) had no haemolytic activity. Strains WUSS417 and WUSS415 have sly gene but without hemolytic phenotype, and no expression or low expression of sly gene may be one explaination; strain WUSS401with sly nonsense mutation has hemolytic activity, which suggested that it may contain other hemolytic factors. The results of zebrafish infection experiment showed that the mortality rates in the groups infected with strains WUSS401, WUSS417, and WUSS013 were 86.6-93.3%. 

[1] Segura M, Fittipaldi N, Calzas C, Gottschalk M. Critical Streptococcus suis Virulence Factors: Are

They All Really Critical?[J]. Trends Microbiol, 2017, 25(7):585-599.

[2] Feng Y, Zhang H, Wu Z, Wang S, Cao M, Hu D, Wang C. Streptococcus suis infection: an

emerging/reemerging challenge of bacterial infectious diseases?[J]. Virulence, 2014, 5(4):477-497.

[3] Gottschalk M, Xu J, Calzas C, Segura M. Streptococcus suis: a new emerging or an old neglected

zoonotic pathogen?[J]. Future microbiology, 2010, 5(3).

[4] Goyette-Desjardins G, Auger JP, Xu J, Segura M, Gottschalk M. Streptococcus suis, an important

pig pathogen and emerging zoonotic agent-an update on the worldwide distribution based on serotyping

and sequence typing[J]. Emerging microbes & infections, 2014, 3(6).

[5] Okura M, Osaki M, Nomoto R, Arai S, Osawa R, Sekizaki T, Takamatsu D. Current Taxonomical

Situation of Streptococcus suis[J]. Pathogens. 2016, 5(3):45.

[6] Hatrongjit R, Kerdsin A, Gottschalk M, Takeuchi D, Hamada S, Oishi K, Akeda Y. First human

case report of sepsis due to infection with Streptococcus suis serotype 31 in Thailand[J]. BMC Infectious

Diseases, 2015, 15(1).

[7] Wu Z, Wang W, Tang M, Shao J, Dai C, Zhang W, Fan H, Yao H, Zong J, Chen D, Wang J, Lu C.

Comparative genomic analysis shows that Streptococcus suis meningitisisolate SC070731 contains a

unique 105K genomic island[J]. Gene, 2014, 535(2):156-164

[8] Williams D M, Lawson G H K, Rowland A C. Streptococcal Infection in Piglets: The Palatine

Tonsils as Portals of Entry for Streptococcus suis[J]. W.B. Saunders, 1973,15(3).

[9] Dennis C H, Kyoung-Jin Y, Jeffrey J Z. A review of porcine tonsils in immunity and disease[J].

Animal Health Research Reviews, 2003,4(2).

[10] Pena Cortes L C, LeVeque R M, Funk J, Marsh T L, Mulks M H. Development of the tonsillar

microbiome in pigs from newborn through weaning[J]. BMC microbiology, 2018,18(1).

[11] Staats JJ, Feder I, Okwumabua O, Chengappa MM. Streptococcus Suis: Past and Present[J].

Veterinary Research Communications, 1997, 21(6):381-407.

[12] Gottschalk M, Segura M, Xu J. Streptococcus suis infections in humans: the Chinese experience

and the situation in North America[J]. Animal health research reviews, 2007,8(1).

[13] Yu H, Jing H, Chen Z, Zheng H, Zhu X, Wang H, Wang S, Liu L, Zu R, Luo L, Xiang N, Liu H,

Liu X, Shu Y, Lee S S, Chuang S K, Wang Y, Xu J, Yang W. Human Streptococcus suis outbreak, Sichuan, China[J]. Emerging infectious diseases, 2006, 12(6).

[14] 吴超. 猪链球菌流行病学特征和hp0197基因多态性研究[D]. 武汉：华中农业大学, 2013.

Wu C. Epidemiological characteristics and hp0197 gene polymorphism of Streptococcus suis[D]. Wuhan：Huazhong Agricultural University,2013(in Chinese with English abstract).

[15] Zigong W, Ran L, Anding Z. Characterization of Streptococcus suis isolates from the diseased

pigs in China between 2003 and 2007[J]. Veterinary Microbiology, 2008,137(1).

[16] 魏子贡. 猪链球菌流行病学及其生物被膜形成机理研究[D]. 武汉：华中农业大学, 2010.

Wei Z G. Research on the epidemiology of Streptococcus suis and the mechanism of its biofilm formation[D]. Wuhan：Huazhong Agricultural University,2010(in Chinese with English abstract).

[17] 黄小武, 黄溢泓, 韦正吉. 2006-2007年柳州市猪屠宰场猪链球菌流行情况调查[J]. 养殖与饲

料, 2010，(10):28-29.

Huang X H，Huang Y H，Wei Z J. Survey on the prevalence of Streptococcus suis in pig slaughterhouses in Liuzhou City, 2006-2007[J]. Farming and Feed, 2010, (10):28-29(in Chinese with English abstract).

[18] 余炜烈. 华南地区屠宰猪群中猪链球菌的流行病学调查及地方株的特性研究[D]. 南京：南京

农业大学, 2007.

Yu W L. Epidemiological survey and characterization of endemic strains of Streptococcus suis in slaughter pigs in southern China[D]. Nanjing: Nanjing Agricultural University,2007(in Chinese with English abstract).

[19] 应薇芳, 赵焕灿, 钱娅, 方维焕. 浙江部分地区屠宰场待宰猪链球菌的检测及药敏试验[J]. 动

物医学进展, 2007, 28(06):24-27.

Yin W F，Zhao H C，Qian Y, Fang W H. Detection and drug sensitivity tests of Streptococcus suis. in pigs awaiting slaughter in some slaughterhouses in Zhejiang[J]. Advances in Animal Medicine, 2007, 28(06): 24-27 (in Chinese with English abstract).

[20] 王楷宬, 熊忠良, 尚延明, 黄保续, 汤明, 谭世君, 张东, 蔡振鸿, 范伟兴. 重庆地区表观健康

猪中猪链球菌的检测[J]. 畜牧兽医学报, 2010, 41(05): 594-599.

Wang K C, Xiong Z L, Shang Y M, Huang B X, Tang M, Tan S J, Zhang D, Cai Z H. Detection of Streptococcus suis in apparently healthy pigs in Chongqing[J]. Journal of Animal Husbandry and Veterinary Medicine, 2010, 41(05): 594-599(in Chinese with English abstract).

[21] 杨筱薇, 郑升博, 王开功，周碧君, 文明, 袁聪俐, 杨志彪, 崔立. 上海屠宰样品中猪链球菌感

染率调查研究[J]. 国外畜牧学(猪与禽), 2010, 30(03): 64-65.

Yang X W, Zheng S B, Wang K G, Zhou B J, Weng M, Yuan C L, Yang Z B, Cui L. A study on the prevalence of Streptococcus suis infection in slaughter samples in Shanghai[J]. Foreign Animal Husbandry (Pigs and Poultry),2010, 30(03): 64-65(in Chinese with English abstract).

[22] 王娟, 贾爱卿, 张炜,王贵平,刘琪,周如月. 广州周边地区健康猪群猪链球菌携带情况调查[J].

中国兽医学报, 2017,37(06):1092-1097.

Wang J, Jia A Q, Zhang W, Wang G P, Liu Q, Zhou R Y. Analysis and epidemiological investigation of Streptococcus suis in Guangzhou surrounding areas[J].2017, 37(06): 1092-1097(in Chinese with English abstract).

[23] 王宇婷,王云光,吴丹丹,周玉龙,范春玲,倪宏波,王新.2007—2015年黑龙江省猪链球菌病分子流

行病学调查[J].黑龙江畜牧兽医,2016(18): 109-111-296.

Wang Y T, Wang Y G, Wu D D, Zhou Y L, Fan C L, Ni H B, Wang X. Molecular epidemiological survey of Streptococcus suis in Heilongjiang Province, 2007-2015[J]. Heilongjiang Animal Husbandry and Veterinary Medicine, 2016(18): 109-111-296. (in Chinese with English abstract).

[24] 周明瑶. 2015年苏南地区健康猪群猪链球菌流行病学调查[D].南京: 南京农业大学, 2016.

Zhou M Y. Epidemiological survey of Streptococcus suis in healthy pig herds in southern

Jiangsu in 2015[D]. Nanjing: Nanjing Agricultural University,2016(in Chinese with English abstract).

[25] 刘琪, 王娟, 周如月, 贾爱卿, 王贵平. 广东地区健康猪群和发病猪群猪链球菌流行病学调查

分析[J]. 中国畜牧兽医, 2017,44(06):1825-1831.

Liu Q, Wang J, Wang R Y, Jia A Q, Wang G P. Epidemiological analysis of Streptococcus suis in

healthy and diseased pig herds in Guangdong[J].China Veterinary Animal Husbandry，2017, 44(06):1825-1831(in Chinese with English abstract).

[26] Zhang B, Ku X, Yu X, Sun Q, Wu H, Chen F, Zhang X, Guo L, Tang X, He Q. Prevalence and

antimicrobial susceptibilities of bacterial pathogens in Chinese pig farms from 2013 to 2017[J]. Scientific Reports, 2019, 9(1).

[27] Ma Z, Zhu H, Su Y, Meng Y, Lin H, He K, Fan H. Identification of two proteins associated with

virulence of Streptococcus suis serotype 2[J]. Infection and immunity, 1991, 59(9).

[28] Goyette-Desjardins G, Auger JP, Xu J, Segura M, Gottschalk M. Streptococcus suis, an important

pig pathogen and emerging zoonotic agent-an update on the worldwide distribution based on

serotyping and sequence typing[J]. Emerging microbes & infections, 2014, 3(6).

[29] Takeuchi D, Kerdsin A, Pienpringam A, Loetthong P, Samerchea S, Luangsuk P, Khamisara K,

Wongwan N, Areeratana P, Chiranairadul P, Lertchayanti S, Petcharat S, Yowang A , Chaiwongsan P, Nakayama T, Akeda Y, Hamada S, Sawanpanyalert P, Dejsirilert S, Oishi K. Population-Based Study of Streptococcus suis Infection in Humans in Phayao Province in Northern Thailand[J]. PLOS ONE, 2012, 7(2).

[30] Hui AC, Ng KC, Tong PY, Mok V, Chow KM, Wu A, Wong LK. Bacterial meningitis in Hong

Kong: 10-years' experience[J]. Clin Neurol Neurosurg, 2005, 107(5):366-370.

[31] 夏胜利. 人重症感染感染2型猪链球菌病研究进展[J]. 现代预防医学, 2009, 36(02):356-358.

Xia S Y. Advances in the study of human severe infection with Streptococcus suis serotype 2[J]. Modern preventive medicine, 2009, 36(02):356-358 (in Chinese with English abstract).

[32] 聂为民，周先志. 人感染猪链球菌病[J]. 人民军医, 2005(09):533-536.

Nie W M, Zhou X Z. Streptococcus suis infection humans[J]. People's Army Medicine，2005，(09):533-536(in Chinese with English abstract).

[33] 胡晓抒，朱凤才，汪华，陈宋义，王广和. 人猪链球菌感染性综合征研究[J]. 中华预防医学

杂志, 2000(03):23-25.

Hu X S, Zhu F C, Wang H, Cheng S Y, Wang G H. Research of Streptococcus suis in humans infectious syndrome[J]. Chinese Journal of Preventive Medicine, 2005，(09):533-536.

[34] 林桢, 黄林光, 梁家习, 韦文相, 黄亚铭. 广西巴马县人感染猪链球菌病2例死亡病例调查分

析[J]. 医学动物防制, 2020, 36(10):996-998.

Lin Z，Huang L G，Liang J X，Wei W X. Investigation and analysis of two fatal cases of human streptococcus suis disease in Bama County, Guangxi[J]. Medical animal control，2020, 36(10):996-998(in Chinese with English abstract).

[35] 贺子翔, 夏昕, 覃玉芳, 杨浩, 覃迪, 向星宇, 胡俊忠, 湛志飞. 湖南省首例猪链球菌14型人

源分离株鉴定及毒力基因分析[J]. 中国人兽共患病学报, 2020,36(08):631-635

He Z X, Xia X, Qin Y F, Yang H, Tan D, Xiang X Y, Hu Z J, Zhan Z F .Identification and virulence gene analysis of the first human isolate of Streptococcus suis serotype 14 in Hunan Province[J]. Chinese Journal of Human-Veterinary Diseases, 2020, 36(08):631-635(in Chinese with English abstract).

[36] 萧松建, 周奕, 张楚东, 方艳梅, 黄辉涛. 一例14型人感染猪链球菌病例流行病学调查[J]. 疾

病监测, 2019, 34(09):861-864.

Xiao S J, Zhou Y, Zhang C D, Fang Y M, Huang H T. Epidemiological investigation of a case of human Streptococcus suis serotype 14 infection[J]. Disease surveillance, 2019, 34(09):861-864(in Chinese with English abstract).

[37] 马涛, 刘艳, 王璇, 孙凤霞, 王建, 杜雪飞, 徐庆, 谢国祥, 林丹, 张敏. 南京市首例人感染猪

链球菌病例调查[J]. 现代预防医学, 2019, 46(16):3042-3044.

Ma T, Liu Y, Wang X,Sun X F, Wang J, Du X F, Xu Q, Xie G X, Lin D, Zhang M. Investigation of the first human case of Streptococcus suis infection in Nanjing[J]. Modern preventive medicine, 2019, 46(16):3042-3044(in Chinese with English abstract).

[38] 赵展庆, 金玉明, 何振扬, 周小敏, 吴艳秋, 符月珍. 脾切除后合并人感染猪链球菌病休克型

1例[J]. 广东医学, 2017, 38(24):38-67.

Zhao Z Q, Jing Y M, He Z Y, Zhou X M, Wu Y Q, Fu Y Z. A case of post-splenectomy combined with human streptococcus suis shock type[J]. Guangdong Medicine，2017, 38(24):38-67(in Chinese with English abstract).

[39] Hatrongjit R, Kerdsin A, Gottschalk M, Takeuchi D, Hamada S, Oishi K, Akeda Y. First human

case report of sepsis due to infection with Streptococcus suis serotype 31 in Thailand[J]. BMC infectious

diseases, 2015, 15.

[40] Goyette-Desjardins G, Auger JP, Xu J, Segura M, Gottschalk M. Streptococcus suis, an important

pig pathogen and emerging zoonotic agent-an update on the worldwide distribution based on serotyping and sequence typing[J]. Emerging microbes & infections, 2014, 3(6).

[41] Wang M, Du P, Wang J, Lan R, Huang J, Luo M, Jiang Y, Zeng J, Quan Y, Shi Z, Zheng H.

Genomic Epidemiology of Streptococcus suis Sequence Type 7 Sporadic Infections in the Guangxi Zhuang Autonomous Region of China[J]. Pathogens, 2019, 8(4).

[42] Huang W, Wang M, Hao H, Yang R, Xie J, Su J, Lin M, Cui Y, Jiang Y. Genomic epidemiological

investigation of a Streptococcus suis outbreak in Guangxi, China, 2016[J]. Infection, genetics and

evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2019,

6(8).

[43] Du P, Zheng H, Zhou J, Lan R, Ye C, Jing H, Jin D, Cui Z, Bai X, Liang J, Liu J, Xu L, Zhang W,

Chen C, Xu J. Detection of Multiple Parallel Transmission Outbreak of Streptococcus suis Human Infection by Use of Genome Epidemiology, China, 2005[J]. Emerging infectious diseases, 2017, 23(2).

[44] Hatrongjit R, Fittipaldi N, Gottschalk M, Kerdsin A. Tools for Molecular Epidemiology of

Streptococcus suis[J]. Pathogens, 2020, 9(2).

[45] Wileman TM, Weinert LA, Howell KJ, Wang J, Peters SE, Williamson SM, Wells JM, Langford

PR, Rycroft AN, Wren BW, Maskell DJ, Tucker AW. Pathotyping the Zoonotic Pathogen Streptococcus suis: Novel Genetic Markers To Differentiate Invasive Disease-Associated Isolates from Non-Disease-Associated Isolates from England and Wales[J]. J Clin Microbiol, 2019, 57(7).

[46] King SJ, Leigh JA, Heath PJ, Luque I, Tarradas C, Dowson CG, Whatmore AM. Development of a

multilocus sequence typing scheme for the pig pathogen Streptococcus suis: identification of virulent

clones and potential capsular serotype exchange[J]. Journal of clinical microbiology, 2002, 40(10).

[47] 郑翰. 分析ST1型与ST7型猪链球菌在临床与实验室方面的差异[D].北京: 中国疾病预防控制

中心, 2008.

Zheng H. Analysis of the clinical and laboratory differences between ST1 and ST7 Streptococcus suis[D]. Beijing：Chinese Centre for Disease Control and Prevention, 2008 (in Chinese with English abstract).

[48] Larsen MV, Cosentino S, Rasmussen S, Friis C, Hasman H, Marvig RL, Jelsbak L,

Sicheritz-Pontén T, Ussery DW, Aarestrup FM, Lund O. Multilocus sequence typing of

total-genome-sequenced bacteria[J]. Journal of clinical microbiology, 2012, 50(4).

[49] Kerdsin A, Akeda Y, Takeuchi D, Dejsirilert S, Gottschalk M, Oishi K. Genotypic diversity of

Streptococcus suis strains isolated from humans in Thailand[J]. European Journal of Clinical

Microbiology & Infectious Diseases, 2018, 37(5).

[50] Oh Y, Tark D, Moon SH, Han JI, Kim WI, Cho HS. Sepsis Caused by Streptococcus suis Serotype

2 in a Eurasian River Otter (Lutra) in the Republic of Korea[J]. Journal of wildlife diseases, 2018, 54(4).

[51] Zheng H, Ji S, Lan R, Liu Z, Bai X, Zhang W, Gottschalk M, Xu J. Population analysis of

Streptococcus suis isolates from slaughtered swine by use of minimum core genome sequence typing[J].

Journal of clinical microbiology, 2014, 52(10).

[52] 邱小彤. 猪链球菌新cps基因簇分析及其高通量检测方法的建立[D]. 北京：中国疾病预防控

制中心, 2017.

Qiu X T. Analysis of new cps gene clusters in Streptococcus suis and the development of its high-throughput detection method[D]. Beijing: Chinese Centre for Disease Control and Prevention, 2017 (in Chinese with English abstract).

[53] Zheng H, Ji S, Lan R, Liu Z, Bai X, Zhang W, Gottschalk M, Xu J. Population analysis of

Streptococcus suis isolates from slaughtered swine by use of minimum core genome sequence typing[J].

Journal of clinical microbiology, 2014, 52(10).

[54] Liu Z, Zheng H, Gottschalk M, Bai X, Lan R, Ji S, Liu H, Xu J. Development of multiplex PCR

assays for the identification of the 33 serotypes of Streptococcus suis[J]. PLoS ONE, 2017, 8(8).

[55] Baums CG, Kaim U, Fulde M, Ramachandran G, Goethe R, Valentin-Weigand P. Identification of

a novel virulence determinant with serum opacification activity in Streptococcus suis[J]. Infection and

immunity, 2006, 74(11).

[56] Takamatsu D, Nishino H, Ishiji T, Ishii J, Osaki M, Fittipaldi N, Gottschalk M, Tharavichitkul P,

Takai S, Sekizaki T. Genetic organization and preferential distribution of putative pilus gene clusters

in Streptococcus suis[J]. Veterinary Microbiology, 2009, 138(1).

[57] Babu KN, Rajesh MK, Samsudeen K, Minoo D, Suraby EJ, Anupama K, Ritto P. Randomly

amplified polymorphic DNA (RAPD) and derived techniques[J]. Methods in molecular biology, 2014,

11(15).

[58] Chatellier S, Gottschalk M, Higgins R, Brousseau R, Harel J. Relatedness of Streptococcus suis

serotype 2 isolates from different geographic origins as evaluated by molecular fingerprinting and

phenotyping[J]. J Clin Microbiol, 1999, 37(2): 362-366.

[59] Martinez G, Harel J, Lacouture S, Gottschalk M. Genetic diversity of Streptococcus suis serotypes

2 and 1/2 isolates recovered from carrier pigs in closed herds[J]. Can J Vet Res, 2002, 66(4):240-248.

[60] Cloutier G, D'Allaire S, Martinez G, Surprenant C, Lacouture S, Gottschalk M. Epidemiology of

Streptococcus suis serotype 5 infection in a pig herd with and without clinical disease[J]. Vet Microbiol,

2003, 97(1-2): 135-151.

[61] 聂小想, 沈志强, 崔言顺, 逄媛, 管宇, 沈旭. 脉冲场凝胶电泳技术在猪链球菌分型中的应用

[J]. 动物医学进展, 2008, (01):70-73.

Nie X X, Sheng Z Y, Cui Y S, Jiang Y, Guan Y, Sheng X. Application of pulsed-field gel electrophoresis in the typing of Streptococcus suis[J]. Advances in Animal Medicine, 2008, (01): 70-73(in Chinese with English abstract).

[62] Vela AI, Goyache J, Tarradas C, Luque I, Mateos A, Moreno MA, Borge C, Perea JA, Domínguez

L, Fernández-Garayzábal JF. Analysis of genetic diversity of Streptococcus suis clinical isolates from

pigs in Spain by pulsed-field gel electrophoresis[J]. Journal of clinical microbiology, 2003, 41(6).

[63] Berthelot-Hérault F, Marois C, Gottschalk M, Kobisch M. Genetic diversity of Streptococcus suis

strains isolated from pigs and humans as revealed by pulsed-field gel electrophoresis[J]. Journal of

clinical microbiology, 2002, 40(2).

[64] Allgaier A, Goethe R, Wisselink HJ, Smith HE, Valentin-Weigand P. Relatedness of Streptococcus

suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and

expression of potential virulence traits[J]. Journal of clinical microbiology, 2001, 39(2).

[65] Rehm T, Baums CG, Strommenger B, Beyerbach M, Valentin-Weigand P, Goethe R. Amplified

fragment length polymorphism of Streptococcus suis strains correlates with their profile of

virulence-associated genes and clinical background[J]. Journal of Medical Microbiology, 2007, 56(1).

[66] 王楷宬, 陆承平, 黄保续, 范伟兴. 猪链球菌荧光DNA扩增片段长度多态性检测方法的建立

[J]. 中国兽医学报, 2012,32(10):1498-1501.

Wang K C, Lu C P, Huang B X, Fan W X. Development of fluorescent amplified fragment length polymorphism for Streptococcus suis[J]. China Veterinary Journal, 2012, 32(10): 1498-1501(in Chinese with English abstract).

[67] Harel J, Higgins R, Gottschalk M, Bigras-Poulin M. Genomic relatedness among reference strains

of different Streptococcus suis serotypes[J]. Canadian journal of veterinary research Revue canadienne

de recherche veterinaire, 1994, 58(4).

[68] 林荣高, 黎满香, 蒋伟, 陈滔. 猪链球菌分子生物学分型方法研究进展[J]. 动物医学进展,

2010, 31(10): 83-87.

Lin R G, Li M X, Jiang W, Chen T. Advances in molecular biology typing methods for Streptococcus suis[J]. Advances in Animal Medicine, 2010, 31(10):83-87 (in Chinese with English abstract).

[69] Okwumabua O, Staats J, Chengappa MM. Detection of genomic heterogeneity in Streptococcus

suis isolates by DNA restriction fragment length polymorphisms of rRNA genes (ribotyping)[J]. Journal

of clinical microbiology, 1995, 33(4).

[70] 王凯. 猪链球菌核糖体基因分型研究[J]. 中国猪业, 2010,5(06):28-30.

Wang K. Genotyping of Streptococcus suis ribosomes[J]. China pig industry, 2010, 5(06):28-30(in Chinese with English abstract).

[71] Staats J J, Plattner B L, Nietfeld J, et al. Use of ribotyping and hemolysin activity to identify highly

virulent Streptococcus suis type 2 isolates[J]. Journal of clinical microbiology, 1998, 36(1).

[72] Li W, Ye C, Jing H, Cui Z, Bai X, Jin D, Zheng H, Zhao A, Xu Y, Gottschalk M, Xu J.

Streptococcus suis outbreak investigation using multiple-locus variable tandem repeat number

analysis[J]. Microbiol Immunol, 2010, 54(7): 380-388.

[73] 李伟. 使用MLVA方法分析暴发相关的猪链球菌[D].北京：中国疾病预防控制中心, 2009.

Li W. Analysis of outbreak-associated Streptococcus suis using the MLVA method[D].Beijing：Chinese Centre for Disease Control and Prevention,2009(in Chinese with English abstract).

[74] 谈忠鸣. 江苏省猪链球菌血清2型菌株耐药性与分子特征研究[D].南京:东南大学, 2015.

Tan M Z. Drug resistance and molecular characterization of Streptococcus suis serotype 2 strains in Jiangsu Province[D]. Nanjing: Southeastern University,2015(in Chinese with English abstract).

[75] Roberts MC. Resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone

antibiotics[J]. Molecular Biotechnology, 2004, 28(1).

[76] 李晓云, 苑青艳, 闫明, 李艳华. 猪链球菌对大环内酯类药物耐药性研究进展[J]. 动物医学进

展, 2008, (06): 80-83.

Li X Y，Yuan Q Y，Yan M, Li Y H. Progress on the Resistance of Streptococcus suis Against Macrolides [J]. Advances in Animal Medicine，2008, (06): 80-83 (in Chinese with English abstract).

[77] 梁圆. ICE在大环内酯类耐药猪链球菌中的分布及其水平转移机制的研究[D]. 南京: 南京农

业大学, 2017.

Liang Y. Reaearch of the distribution of ICE in macrolide resistant Streptococcus suis and its horizontal transfer mechanism[D]. Nanjing: Nanjing Agricultural University, 2017 (in Chinese with English abstract).

[78] Brenciani A, Bacciaglia A, Vecchi M, Vitali LA, Varaldo PE, Giovanetti E. Genetic elements

carrying erm(B) in Streptococcus pyogenes and association with tet(M) tetracycline resistance gene[J].

Antimicrobial agents and chemotherapy, 2007, 51(4).

[79] Leclercq R, Courvalin P. Resistance to macrolides and related antibiotics in Streptococcus

pneumoniae[J]. Antimicrobial agents and chemotherapy, 2002, 46(9).

[80] Martel A, Devriese LA, Decostere A, Haesebrouck F. Presence of macrolide resistance genes in

streptococci and enterococci isolated from pigs and pork carcasses[J]. International Journal of Food

Microbiology, 2003, 84(1).

[81] Palmieri C, Princivalli MS, Brenciani A, Varaldo PE, Facinelli B. Different genetic elements

carrying the tet(W) gene in two human clinical isolates of Streptococcus suis[J]. Antimicrobial agents

and chemotherapy, 2011, 55(2).

[82] Tait-Kamradt A, Clancy J, Cronan M, Dib-Hajj F, Wondrack L, Yuan W, Sutcliffe J. mefE is

necessary for the erythromycin-resistant M phenotype in Streptococcus pneumoniae[J]. Antimicrobial

agents and chemotherapy, 1997, 41(10).

[83] 黄金虎, 刘民星, 商可心. 46株猪链球菌对大环内酯类抗生素的耐药性及PFGE分型[J].

南京农业大学学报, 2013, 36(04):105-110.

Huang J H，Liu M X，Shang K X. Resistance to macrolide antibiotics and PFGE typing of 46 strains of Streptococcus suis[J]. Journal of Nanjing Agricultural University, 2013, 36(04): 105-110(in Chinese with English abstract).

[84] Chopra I, Hawkey PM, Hinton M. Tetracyclines, molecular and clinical aspects[J]. Narnia, 1992,

29(3).

[85] Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and

epidemiology of bacterial resistance [J]. Microbiology and molecular biology reviews, 2001, 65(2).

[86] Paulsen IT, Brown MH, Skurray RA. Proton-dependent multidrug efflux systems[J].

Microbiological reviews, 1996, 60(4).

[87] 冯新，韩文瑜，雷连成. 细菌对四环素类抗生素的耐药机制研究进展[J]. 中国兽药杂志, 2004,

(02): 38-42.

Feng X，Han W Y，Lei L C. Advances in the study of bacterial resistance mechanisms to tetracycline antibiotics[J]. China Veterinary Medicine Journal, 2004, (02): 38-42(in Chinese with English abstract).

[88] Connell SR, Tracz DM, Nierhaus KH, Taylor DE. Ribosomal protection proteins and their

mechanism of tetracycline resistance[J]. Antimicrobial agents and chemotherapy, 2003, 47(12).

[89] Chen L, Song Y, Wei Z, He H, Zhang A, Jin M. Antimicrobial Susceptibility, Tetracycline and

Erythromycin Resistance Genes, and Multilocus Sequence Typing of Streptococcus suis Isolates from

Diseased Pigs in China[J]. Janpanese society of veterinary science, 2013 ,75(5).

[90] Palmieri C, Magi G, Mingoia M, Bagnarelli P, Ripa S, Varaldo PE, Facinelli B. Characterization of

a Streptococcus suis tet(O/W/32/O)-carrying element transferable to major streptococcal pathogens[J]. Antimicrob Agents Chemother, 2012, 56(9): 4697-4702.

[91] Tang F, Bossers A, Harders F, Lu C, Smith H. Complete Genome Sequence of the Streptococcus

suis Temperate Bacteriophage ?NJ2 [J]. Genome Announc, 2013, 1(1).

[92] 杨建江,韩文瑜,雷连成,杜锐,王兴龙,江文正. 猪链球菌耐药性的检测[J]. 中国兽医科技,

2004(07): 48-50.

Yang J J, Han W Y, Lei L C, Du R, Wang X L, Wang W Z. Determination of drug resistance in Streptococcus suis isolates [J]. China Veterinary Science and Technology, 2004, (07): 48-50(in Chinese with English abstract).

[93] 褚美芬,倪柏锋,孙琦,朱家新,徐辉. 浙江省某猪场暴发II型猪链球菌感染及病原诊断和药敏试

验[J]. 微生物学杂志, 2004, (05): 126-128.

Zhu M F, Ni B F, Sun Q, Zhu J X, Xu H. Outbreak of type II Streptococcus suis infection in a pig farm in Zhejiang Province and pathogenic diagnosis and drug sensitivity testing[J]. Journal of Microbiology, 2004, (05): 126-128 (in Chinese with English abstract).

[94] 王丽平,陆承平,唐家琪. 猪链球菌对大环内酯类抗生素的耐药性及耐药表型[J]. 南京农业大学

学报, 2004, (04):81-84.

Wang L P, Lu C P, Tang J Q. Trends and phenotypes of resistance to macrolides in Streptococcus suis[J]. Journal of Nanjing Agricultural University, 2004, (04): 81-84(in Chinese with English abstract).

[95] 应薇芳, 赵焕灿, 钱娅,方维焕. 浙江部分地区屠宰场待宰猪链球菌的检测及药敏试验[J]. 动

物医学进展, 2007, (06): 24-27.

Yin W F, Zhao H C, Qian Ya, Fang W H. Detection and drug sensitivity tests of Streptococcus suis. awaiting slaughter in some slaughterhouses in Zhejiang[J]. Advances in Animal Medicine, 2007， (06): 24-27 (in Chinese with English abstract).

[96] Zhang C, Ning Y, Zhang Z, Song L, Qiu H, Gao H. In vitro antimicrobial susceptibility of

Streptococcus suis strains isolated from clinically healthy sows in China[J].Veterinary Microbiology,

2008, 131(3).

[97] 沈萍, 黎满香. 猪链球菌2型及7型分离株对16种抗生素的耐药性分析[J]. 安徽农业科学,

2009, 37(01): 140-141.

Sheng P, Li M X. Analysis of the resistance of Streptococcus suis serotype 2 and serotype 7 isolates to 16 antibiotics[J]. AnHui Agricultural Science, 2009, 37(01): 140-141(in Chinese with English abstract).

[98] 苑青艳. 猪链球菌对氟喹诺酮类药物耐药性与耐药基因的研究[D].哈尔滨：东北农业大学,

2009.

Yuan Q Y. Research of fluoroquinolone resistance and drug resistance genes in Streptococcus suis[D]. Haerbing: Northeast Agricultural University, 2009 (in Chinese with English abstract).

[99] 邢娟, 李学瑞, 柳纪省, 胡永浩. 甘肃省健康猪群猪链球菌分离株的耐药性检测[J]. 贵州农业

科学, 2011, 39(02): 128-131.

Xin J, Li X R, Liu J S, Hu Y H. Detection of drug resistance of Streptococcus suis isolates from healthy pig herds in Gansu Province[J]. Guizhou Agricultural Science, 2011,39(02):128-131. (in Chinese with English abstract).

[100] Zhang C, Zhang P, Wang Y, Fu L, Liu L, Xu D, Hou Y, Li Y, Fu M, Wang X, Wang S, Ding S,

Shen Z. Capsular serotypes, antimicrobial susceptibility, and the presence of transferable oxazolidinone

resistance genes in Streptococcus suis isolated from healthy pigs in China[J]. Vet Microbiol, 2020,24(7):

108-750.

[101] Zhang B, Ku X, Yu X, Sun Q, Wu H, Chen F, Zhang X, Guo L, Tang X, He Q. Prevalence and

antimicrobial susceptibilities of bacterial pathogens in Chinese pig farms from 2013 to 2017[J]. Sci Rep, 2019, 9(1): 9-908.

[102] Zhang C, Zhang P, Wang Y, Fu L, Liu L, Xu D, Hou Y, Li Y, Fu M, Wang X, Wang S, Ding S,

Shen Z. Capsular serotypes, antimicrobial susceptibility, and the presence of transferable oxazolidinone

resistance genes in Streptococcus suis isolated from healthy pigs in China[J]. Vet Microbiol, 2020, 247:

108-750.

[103] 杜凡姝, 吕茜, 段锻, 陈丽，黄金虎. 江苏苏北地区猪链球菌耐药性调查及万古霉素耐药基

因检测[J]. 畜牧与兽医, 2018, 50(12): 32-36.

Du F S, Lv Q, Duan D, Chen L，Huang J H. Investigation of drug resistance of Streptococcus suis and vancomycin resistance gene detection in northern Jiangsu[J]. Livestock and Veterinary Medicine, 2018, 50(12):32-36 (in Chinese with English abstract).

[104] 王长珍, 刘文宇, 祝瑶, 栾天，于淼，杨亲，刘思国. 2017年我国4个省份屠宰场猪链球菌

的分离鉴定及耐药性分析[J]. 中国预防兽医学报, 2019, 41(12): 1210-1214.

Wang C Z, Liu W Y, Zhu Y, Luan T, Yu M, Yang Q, Liu S G. Isolation and identification of Streptococcus suis from slaughterhouses in four provinces in China and analysis of drug resistance in 2017[J]. Chinese Journal of Preventive Veterinary Medicine, 2019, 41(12): 1210-1214(in Chinese with English abstract).

[105] Reusser F. Effect of lincomycin and clindamycin on peptide chain initiation[J]. Antimicrob Agents

Chemother, 1975, 7(1): 32-37.

[106] Bojarska A, Molska E, Janas K, Skoczyńska A, Stefaniuk E, Hryniewicz W, Sadowy E.

Streptococcus suis in invasive human infections in Poland: clonality and determinants of virulence and

antimicrobial resistance[J]. Eur J Clin Microbiol Infect Dis, 2016, 35(6): 917-925.

[107] Zhao Q, Wendlandt S, Li H, Li J, Wu C, Shen J, Schwarz S, Wang Y. Identification of the novel

lincosamide resistance gene lnu(E) truncated by ISEnfa5-cfr-ISEnfa5 insertion in Streptococcus suis: de

novo synthesis and confirmation of functional activity in Staphylococcus aureus[J]. Antimicrob Agents

Chemother, 2014, 58(3): 1785-1788.

[108] Holden MT, Hauser H, Sanders M, Ngo TH, Cherevach I, Cronin A, Goodhead I, Mungall K,

Quail MA, Price C, Rabbinowitsch E, Sharp S, Croucher NJ, Chieu TB, Mai NT, Diep TS, Chinh NT,

Kehoe M, Leigh JA, Ward PN, Dowson CG, Whatmore AM, Chanter N, Iversen P, Gottschalk M, Slater

JD, Smith HE, Spratt BG, Xu J, Ye C, Bentley S, Barrell BG, Schultsz C, Maskell DJ, Parkhill J. Rapid

evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis[J].

PLoS One, 2009, 4(7): 60-72.

[109] Gurung M, Tamang MD, Moon DC, Kim SR, Jeong JH, Jang GC, Jung SC, Park YH, Lim SK.

Molecular Basis of Resistance to Selected Antimicrobial Agents in the Emerging Zoonotic Pathogen

Streptococcus suis[J]. J Clin Microbiol, 2015, 53(07): 2332-2336.

[110] 王晓旭，宁昆, 徐锋, 沈莉萍, 张维谊. 上海市150株猪链球菌对8种常见抗菌药物的耐药

情况[J]. 中国动物检疫, 2018, 35(09): 27-31.

Wang X X, Ning K, Xu F, Zhang W Y. Resistance of 150 strains of Streptococcus suis to 8 common antimicrobial drugs in Shanghai[J]. China Animal Quarantine, 2018, 35(09): 27-31(in Chinese with English abstract).

[111] Ge Y, Wu J, Xia Y, Yang M, Xiao J, Yu J. Molecular Dynamics Simulation of the Complex

PBP-2x with Drug Cefuroxime to Explore the Drug Resistance Mechanism of Streptococcus suis R61[J].

PLOS ONE, 2012, 7(4).

[112] Huang J, Chen L, Li D, Wang M, Du F, Gao Y, Wu Z, Wang L. Emergence of a vanG-carrying

and multidrug resistant ICE in zoonotic pathogen Streptococccus suis[J]. Vet Microbiol, 2018, 22(2): -

109-113.

[113] 王长珍. 多重耐药基因optrA在猪链球菌中的流行特点及防控策略[D].北京：中国农业科学

院, 2020.

Wang C Z. Epidemiological characteristics of the multidrug resistance gene optrA in Streptococcus suis and strategies for prevention and control[D]. Beijing：Chinese Academy of Agricultural Sciences, 2020(in Chinese with English abstract).

[114] Wang Y, Li D, Song L, Liu Y, He T, Liu H, Wu C, Schwarz S, Shen J. First report of the

multiresistance gene cfr in Streptococcus suis[J]. Antimicrob Agents Chemother, 2013, 57(8):

4061-4063.

[115] 商艳红. 耐药基因optrA和lsa（E）在猪源肠球菌和链球菌中流行及传播机制的研究[D]. 西

安：西北农林科技大学, 2019.

Shang YH Prevalence and transmission mechanisms of drug-resistant genes optrA and lsa(E) in enterococci and streptococci of porcine origin[D]. Xian：Northwest Agriculture and Forestry University,2019(in Chinese with English abstract).

[1] Ma J, Liu J, Zhang Y, Wang D, Liu R, Liu G, Yao H, Pan Z. Bacitracin resistance and enhanced

virulence of Streptococcus suis via a novel efflux pump[J]. BMC Veterinary Research, 2019,

15(1):377.

[2] Wu Z, Wang W, Tang M, Shao J, Dai C, Zhang W, Fan H, Yao H, Zong J, Chen D, Wang J, Lu C. Comparative genomic analysis shows that Streptococcus suis meningitis isolate SC070731 contains a unique 105K genomic island[J].Gene, 2014, 535(2):156-164

[3] Higgins R, Gottschalk M, Mittal KR, Beaudoin M. Streptococcus suis infection in swine. A sixteen month study[J]. Can J Vet Res, 1990, 54(1):170-173.

[4] Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis: the unresolved questions[J]. Vet Microbiol, 2000, 76(3):259-272.

[5] Swildens B, Nielen M, Wisselink HJ, Verheijden JH, Stegeman JA. Elimination of strains of Streptococcus suis serotype 2 From the tonsils of carrier sows by combined medication and vaccination[J].Vet Rec, 2007, 160(18):619-621.

[6] Arends JP, Hartwig N, Rudolphy M, Zanen HC. Carrier rate of Streptococcus suis capsular serotype 2 in palatine tonsils of slaughtered pigs[J]. J Clin Microbiol, 1984, 20(5):945-947.

[7] Ngo TH, Tran TB, Tran TT, Nguyen VD, Campbell J, Pham HA, Huynh HT, Nguyen VV, Bryant JE, Tran TH, Farrar J, Schultsz C. Slaughterhouse pigs are a major reservoir of Streptococcus suis Serotype 2 capable of f causing human infection in southern Vietnam[J]. PLoS One，2011，6(3)

[8] 高雪萍. 江苏某市屠宰场猪链球菌流行病学调查及NCLs菌株病原特性分析[D].南京：南京农业大学, 2018.

Gao X P. The Epidemiological investigation of streptococcus suis isolate from Slaughterhouse in Jiangsu Province and the analysis of pathogenic characteristics of NCLs Strains[D]. Nanjing： Nanjing Agricultural University, 2018 (in Chinese with English abstract).

[9] 陈浩.猪链球菌新荚膜基因簇（NCL）菌株分离鉴定及NCL4菌株WUSS351基因组分析[D]. 南京: 南京农业大学, 2019.

Chen H. Isolation and identification of streptococcus suis NCL and Strains and Genomic Analysis of NCL4 Strains WUSS351[D]. Nanjing: Nanjing Agricultural University, 2019(in Chinese with English abstract).

[10] Pan Z, Ma J, Dong W, Song W, Wang K, Lu C, Yao H. Novel variant serotype of streptococcus suis isolated from piglets with meningitis[J]. Applied and environmental microbiology, 2015, 81(3).

[11] Breton J, Mitchell W R, Rosendal S. Streptococcus suis in slaughter pigs and abattoir workers[J]. Can J Vet Res, 1986, 50(3):338-341.

[12] Arends JP, Zanen HC. Meningitis caused by Streptococcus suis in humans[J]. Rev Infect Dis, 1988, 10(1):131-137.

[13] Nghia HD, Tu le TP, Wolbers M, Thai CQ, Hoang NV, Nga TV, Thao le TP, Phu NH, Chau TT, Sinh DX, Diep TS, Hang HT, Truong H, Campbell J, Chau NV, Chinh NT, Dung NV, Hoa NT, Spratt BG, Hien TT, Farrar J, Schultsz C. Risk factors of Streptococcus suis infection in Vietnam. A case-control study[J]. PLoS One, 2011, 6(3):17604.

[14] Segura M, Fittipaldi N, Calzas C, Gottschalk M. Critical Streptococcus suis Virulence Factors: Are They All Really Critical?[J]. Trends Microbiol, 2017, 25(7):585-599.

[15] 沈艳玲.猪链球菌血清31型致病与耐药特征[D]. 南京：南京农业大学, 2020.

Shen Y L. The pathogenicity and antimicrobial resistance characteristics of streptococcus suis serotype 31[D]. Nanjing：Nanjing Agricultural University, 2020(in Chinese with English abstract).

[16] 王楷宬, 熊忠良, 尚延明, 黄保续, 汤明, 谭世君, 张东, 蔡振鸿, 范伟兴. 重庆地区表观健康猪中猪链球菌的检测[J]. 畜牧兽医学报, 2010, 41(05):594-599.

Wang K C, Xiong Z L, Shang Y M, Huang B X, Tang M, Tan S J, Zhang D, Cai H Z, Fan W X. Detection of Streptococcus suis in apparently healthy pigs in Chongqing Provine[J]. Journal of Animal Husbandry and Veterinary Medicine, 2010, 41(05):594-599.

[17] 应薇芳, 赵焕灿, 钱娅,方维焕.浙江部分地区屠宰场待宰猪链球菌的检测及药敏试验[J]. 动物医学进展, 2007, (06):24-27.

Yin W F，Zhao H C，Qian Y, Fang W H. Detection and drug sensitivity tests of Streptococcus suis in pigs awaiting slaughter in some slaughterhouses in Zhejiang[J]. Advances in Animal Medicine，2007(06):24-27(in Chinese with English abstract).

[18] 周明瑶. 2015年苏南地区健康猪群猪链球菌流行病学调查[D]. 南京：南京农业大学, 2016.：88–90

Zhou M Y. Epidemiological survey of Streptococcus suis in healthy pig herds in southern Jiangsu in 2015[D]. Nanjing：Nanjing Agricultural University,2016:88–90 (in Chinese with English abstract).

[19] Thongkamkoon P, Kiatyingangsulee T, Gottschalk M. Serotypes of Streptococcus suis isolated from healthy pigs in Phayao Province, Thailand[J]. Bmc Research Notes, 2017, 10(1):53.

[1] Tien LHT, Nishibori T, Nishitani Y, Nomoto R, Osawa R. Reappraisal of the taxonomy of Streptococcus suis serotypes 20, 22, 26, and 33 based on DNA-DNA homology and sodA and recN phylogenies[J]. Vet Microbiol, 2013, 162(2-4):842-849.

[2] Goyette-Desjardins G, Auger JP, Xu J, Segura M, Gottschalk M. Streptococcus suis, an important pig pathogen and emerging zoonotic agent-an update on the worldwide distribution based on serotyping and sequence typing[J]. Emerg Microbes Infect, 2014, 3(6)

[3] Rieckmann K, Seydel A, Szewczyk K, Klimke K, Rungelrath V, Baums CG. Streptococcus suis cps7: an emerging virulent sequence type (ST29) shows a distinct, IgM-determined pattern of bacterial survival in blood of piglets during the early adaptive immune response after weaning[J]. Vet Res, 2018, 49(1):48.

[4] Estrada AA, Gottschalk M, Rossow S, Rendahl A, Gebhart C, Marthaler DG. Serotype and Genotype (Multilocus Sequence Type) of Streptococcus suis Isolates from the United States Serve as Predictors of Pathotype[J]. J Clin Microbiol, 2019, 57(9).

[5] Unterweger C, Ruczizka U, Spergser J, Baums CG, Hennig-Pauka I. Effect of Early-Life Treatment of Piglets with Long-Acting Ceftiofur on Colonization of Streptococcus suis Serotype 7 and Elicitation of Specific Humoral Immunity in a Farm Dealing with Streptococcus Diseases[J]. Pathogens, 2018, 7(2).

[6] Tian Y, Airstrips FM, Lu CP. Characterization of Streptococcus suis serotype 7 isolates from diseased pigs in Denmark[J]. Vet Microbiol, 2004, 103(1-2):55-62.

[7] Silva LM, Baums CG, Rehm T, Wisselink HJ, Goethe R, Valentin-Weigand P.Virulence-associated gene profiling of Streptococcus suis isolates by PCR[J]. Vet Microbiol, 2006, 115(1-3):117-127.

[8] Chen C, Zhang W, Zheng H, Lan R, Wang H, Du P, Bai X, Ji S, Meng Q, Jin D, Liu K, Jing H, Ye C, Gao GF, Wang L, Gottschalk M, Xu J. Minimum core genome sequence typing of bacterial pathogens: a unified approach for clinical and public health microbiology[J]. J Clin Microbiol, 2013,51(8):2582-2591.

[9] Pan X, Ge J, Li M, Wu B, Wang C, Wang J, Feng Y, Yin Z, Zheng F, Cheng G, Sun W, Ji H, Hu D, Shi P, Feng X, Hao X, Dong R, Hu F, Tang J. The orphan response regulator CovR: a globally negative modulator of virulence in Streptococcus suis serotype 2[J]. Journal of bacteriology, 2009, 191(8).

[10] Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S, Cattoir V, Philippon A, Allesoe RL, Rebelo AR, Florensa AF, Fagelhauer L, Chakraborty T, Neumann B, Werner G, Bender JK, Stingl K, Nguyen M, Coppens J, Xavier BB, Malhotra-Kumar S, Westh H, Pinholt M, Anjum MF, Duggett NA, Kempf I, Nyk?senoja S, Olkkola S, Wieczorek K, Amaro A, Clemente L, Mossong J, Losch S, Ragimbeau C, Lund O, Aarestrup FM. ResFinder 4.0 for predictions of phenotypes from genotypes[J]. J Antimicrob Chemother, 2020, 75(12):3491-3500.

[11] Wisselink HJ, Smith HE, Stockhofe-Zurwieden N, Peperkamp K, Vecht U. Distribution of capsular types and production of muramidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis strains isolated from diseased pigs in seven European countries[J].Vet Microbiol,2000, 74(3):237-248.

[12] Boetner A G, Binder M, Bille-Hansen V. Streptococcus suis infections in Danish pigs and

experimental infection with Streptococcus suis serotype 7[J]. Acta Pathol Microbiol Immunol

Scand B, 1987, 95(4):233-239.

[13] Palmieri C, Varaldo P E, Facinelli B. Streptococcus suis, an Emerging Drug-Resistant Animal

and Human Pathogen[J]. Front Microbiol, 2011,2:235.

[14] Wisselink HJ, Veldman KT, Van den Eede C, Salmon SA, Mevius DJ. Quantitative susceptibility of Streptococcus suis strains isolated from diseased pigs in seven European countries to antimicrobial agents licensed in veterinary medicine[J]. Vet Microbiol, 2006, 113(1-2):73-82.

[15] Huang J, Ma J, Shang K, Hu X, Liang Y, Li D, Wu Z, Dai L, Chen L, Wang L. Evolution and Diversity of the Antimicrobial Resistance Associated Mobilome in Streptococcus suis: A Probable Mobile Genetic Elements Reservoir for Other Streptococci[J]. Front Cell Infect Microbiol, 2016, 6:118.