猪链球菌病病原的致病机制研究进展

范红结 ,  刘明星

南京农业大学学报 ›› 2026, Vol. 49 ›› Issue (5) : 1196 -1207.

PDF (2539KB)
南京农业大学学报 ›› 2026, Vol. 49 ›› Issue (5) : 1196 -1207. DOI: 10.7685/jnau.202605005
生物兽药

猪链球菌病病原的致病机制研究进展

作者信息 +

Research progress in the pathogenic mechanism of porcine streptococcosis

Author information +
文章历史 +
PDF (2599K)

摘要

猪链球菌病主要由猪链球菌(Streptococcus suis, SS)和马链球菌兽疫亚种(Streptococcus equi subspecies zooepidemicus, SEZ)感染引起,是一种重要的人兽共患病。发病猪以脑膜炎、败血症、肺炎和关节炎为主要特征。人可通过接触病猪或污染产品等途径感染,引起脑膜脑炎、人链球菌样中毒性休克综合征等病症。目前,我国和东南亚等的养猪地区,SS是猪链球菌病的主要病原,血清2(SS2)、7、9、1型等血清型感染最为常见,以SS2毒力最强;由SEZ引起的猪链球菌病在北美的养猪地区被频繁报道。本文围绕定殖、突破屏障、免疫逃避、扩散及组织损伤等病原菌致病环节,介绍SS2、SEZ主要的相关研究进展,重点包括荚膜、溶血素、脂磷壁酸、自溶素、脑侵袭因子A蛋白、甘露糖特异性磷酸转移酶系统IIC组分和外泌体等关键毒力因子的生物学功能,以及丝氨酸/苏氨酸蛋白激酶、二元调控系统等磷酸化修饰系统的毒力调控作用及机制。最后,对猪链球菌病未来的研究方向进行了展望,以期为全球“减抗、限抗、禁抗”养殖新背景下该病防控新策略的探索提供参考。

Abstract

Porcine streptococcosis is primarily caused by Streptococcus suis (SS) and Streptococcus equi subspecies zooepidemicus (SEZ), which is an important zoonotic disease. Affected pigs are characterized by meningitis, septicemia, pneumonia, and arthritis. Humans can be infected through contact with diseased pigs or contaminated products, leading to meningoencephalitis and streptococcal toxic shock-like syndrome. Currently, SS is the predominant pathogen of porcine streptococcosis in China and other Southeast Asian pig-farming countries with serotype 2, 7, 9, and 1 being the most frequently detected serotypes, and serotype 2 (SS2) isolates exhibit the highest virulence. In contrast, this disease caused by SEZ in North America is frequently reported. This review summarized key research advances on SS2 and SEZ with respect to critical pathogenic processes, including colonization, barrier breakthrough, immune evasion, dissemination, and tissue damage. Emphasis is placed on the biological functions of key virulence factors such as capsule, hemolysin, lipoteichoic acid, autolysin, brain invasion factor A, PTS system mannose-specific transporter subunit IIC, and exosomes, as well as the virulence-regulatory roles of phosphorylation systems including the serine/threonine protein kinase Stk1 and two-component regulatory systems. Furthermore, the contribution of co-infections with other pathogenic microorganisms to the pathogenesis of porcine streptococcosis is discussed. Finally, future research directions are proposed, aiming to provide a reference for the development of novel prevention and control strategies under the global background of antibiotic reduction, restriction, and prohibition in animal farming.

关键词

猪链球菌病 / 致病机制 / 屏障损伤 / 免疫逃逸 / 毒力因子

Key words

porcine streptococcosis / pathogenic mechanism / barrier disruption / immune evasion / virulence factor

引用本文

引用格式 ▾
范红结,刘明星. 猪链球菌病病原的致病机制研究进展[J]. 南京农业大学学报, 2026, 49(5): 1196-1207 DOI:10.7685/jnau.202605005

登录浏览全文

4963

注册一个新账户 忘记密码

参考文献

[1]

Zouharová M, Šimek B, Gebauer J, et al. Characterisation of Streptococcus suis isolates in the Czech republic collected from diseased pigs in the years 2018-2022 [J]. Pathogens, 2022, 12(1): 5.

[2]

王姝优, 华修国, 朱建国, 等. 猪链球菌2型在小型猪模型体内的动态分布[J]. 上海交通大学学报(农业科学版), 2007, 25(4): 337-341, 355.

[3]

Wang S Y, Hua X G, Zhu J G, et al. Dynamic distribution of Streptococcus suis type 2 in mini-swine model [J]. Journal of Shanghai Jiaotong University (Agricultural Science), 2007, 25(4): 337-341, 355 (in Chinese with English abstract).

[4]

Su Y, Zhang Z H, Wang L, et al. Whole-genome sequencing and phenotypic analysis of Streptococcus equi subsp. zooepidemicus sequence type 147 isolated from China [J]. Microorganisms, 2024, 12(4): 824.

[5]

Costa M O, Lange B. Streptococcus equi subspecies zooepidemicus and sudden deaths in swine, Canada [J]. Emerging Infectious Diseases, 2020, 26(10): 2522-2524.

[6]

Haas B, Grenier D. Understanding the virulence of Streptococcus suis: a veterinary, medical, and economic challenge [J]. Médecine et Maladies Infectieuses, 2018, 48(3): 159-166.

[7]

胡晓抒, 朱凤才, 汪华, 等. 人猪链球菌感染性综合征研究[J]. 中华预防医学杂志, 2000, 34(3): 150-152.

[8]

Hu X S, Zhu F C, Wang H, et al. Studies on human streptococcal infectious syndrome caused by infected pigs[J]. Chinese Journal of Preventive Medicine, 2000, 34(3): 150-152 (in Chinese with English abstract).

[9]

Yu H J, Jing H Q, Chen Z H, et al. Human Streptococcus suis outbreak, Sichuan, China [J]. Emerging Infectious Diseases, 2006, 12(6): 914-920.

[10]

Gunatala R, Khamai L, Srisai N, et al. Contamination of Streptococcus suis and S. suis serotype 2 in raw pork and edible pig organs: a public health concern in Chiang Mai, Thailand [J]. Foods, 2024, 13(13): 2119.

[11]

Brizuela J, Kajeekul R, Roodsant T J, et al. Streptococcus suis outbreak caused by an emerging zoonotic strain with acquired multi-drug resistance in Thailand [J]. Microbial Genomics, 2023, 9(2): mgen000952.

[12]

Dong X X, Chao Y J, Zhou Y, et al. The global emergence of a novel Streptococcus suis clade associated with human infections [J]. EMBO Molecular Medicine, 2021, 13(7): EMMM202013810.

[13]

Jiang C S, Zhou P, Zhang X Q, et al. ARF6 promotes Streptococcus suis suilysin induced apoptosis in HBMECs [J]. International Journal of Biological Macromolecules, 2024, 268: 131839.

[14]

Meng Y, Wang Q, Ma Z, et al. Streptococcal autolysin promotes dysfunction of swine tracheal epithelium by interacting with vimentin[J]. PLoS Pathogens, 2022, 18(8): e1010765.

[15]

Ni H, Li M, Wang Q Q, et al. Inactivation of the htpsA gene affects capsule development and pathogenicity of Streptococcus suis [J]. Virulence, 2020, 11(1): 927-940.

[16]

Niu K, Meng Y, Liu M X, et al. Phosphorylation of GntR reduces Streptococcus suis oxidative stress resistance and virulence by inhibiting NADH oxidase transcription [J]. PLoS Pathogens, 2023, 19(3): e1011227.

[17]

Li S, Ma Z, Lin H X, et al. STK-mediated FadR phosphorylation regulates the acid resistance and virulence of Streptococcus suis [J]. PLoS Pathogens, 2025, 21(9): e1013534.

[18]

Shi K D, Li Y, Xu M S, et al. Membrane vesicles derived from Streptococcus suis serotype 2 induce cell pyroptosis in endothelial cells via the NLRP3/Caspase-1/GSDMD pathway [J]. Journal of Integrative Agriculture, 2024, 23(4): 1338-1353.

[19]

Liu X, Lv F, Zhu Y N, et al. PRRSV promotes bacterial infection by remodeling actin cytoskeleton and cell membrane proteins[J]. mBio, 2025, 16(10): e0194525.

[20]

单鑫, 蔺辉星, 周红, 等. 猪链球菌溶血素促进副猪格拉菌突破猪呼吸道上皮屏障的作用研究[J]. 畜牧与兽医, 2026, 58(3): 94-102.

[21]

Shan X, Lin H X, Zhou H, et al. Promoting effect of Streptococcus suis suilysin on the penetration of Glaesserella parasuis to porcine respiratory epithelial barrier [J]. Animal Husbandry & Veterinary Medicine, 2026, 58(3): 94-102 (in Chinese with English abstract).

[22]

Rosan B, Lamont R J. Dental plaque formation[J]. Microbes and Infection, 2000, 2(13): 1599-1607.

[23]

Zhao Q, Maynard C L. Mucus, commensals, and the immune system[J]. Gut Microbes, 2022, 14(1): 2041342.

[24]

Musyoki A M, Shi Z Y, Xuan C L, et al. Structural and functional analysis of an anchorless fibronectin-binding protein FBPS from Gram-positive bacterium Streptococcus suis [J]. Proc Natl Acad Sci USA, 2016, 113(48): 13869-13874.

[25]

Ju C X, Gu H W, Lu C P. Characterization and functional analysis of atl, a novel gene encoding autolysin in Streptococcus suis [J]. Journal of Bacteriology, 2012, 194(6): 1464-1473.

[26]

Li M, Shao Z Q, Guo Y Q, et al. The type II histidine triad protein HtpsC is a novel adhesion with the involvement of Streptococcus suis virulence [J]. Virulence, 2015, 6(6): 631-641.

[27]

Fittipaldi N, Sekizaki T, Takamatsu D, et al. D-alanylation of lipoteichoic acid contributes to the virulence of Streptococcus suis [J]. Infection and Immunity, 2008, 76(8): 3587-3594.

[28]

Gisch N, Auger J P, Thomsen S, et al. Structural analysis and immunostimulatory potency of lipoteichoic acids isolated from three Streptococcus suis serotype 2 strains [J]. Journal of Biological Chemistry, 2018, 293(31): 12011-12025.

[29]

Oki H, Kawahara K, Maruno T, et al. Interplay of a secreted protein with type IV pilus for efficient enterotoxigenic Escherichia coli colonization [J]. Proc Natl Acad Sci USA, 2018, 115(28): 7422-7427.

[30]

Yao H, Li G, Xiong X L, et al. LygA retention on the surface of Listeria monocytogenes via its interaction with wall teichoic acid modulates bacterial homeostasis and virulence [J]. PLoS Pathogens, 2023, 19(6): e1011482.

[31]

Huang X T, Li X Y, An H R, et al. Capsule type defines the capability of Klebsiella pneumoniae in evading Kupffer cell capture in the liver [J]. PLoS Pathogens, 2022, 18(8): e1010693.

[32]

Schembri M A, Dalsgaard D, Klemm P. Capsule shields the function of short bacterial adhesins[J]. Journal of Bacteriology, 2004, 186(5): 1249-1257.

[33]

Kietzman C C, Gao G L, Mann B, et al. Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium[J]. Nature Communications, 2016, 7: 10859.

[34]

Zhang A D, Chen B, Yuan Z Z, et al. HP0197 contributes to CPS synthesis and the virulence of Streptococcus suis via CcpA [J]. PLoS One, 2012, 7(11): e50987.

[35]

Zhong X J, Zhang Y, Zhu Y C, et al. Identification of an autorepressing two-component signaling system that modulates virulence in Streptococcus suis serotype 2 [J]. Infection and Immunity, 2019, 87(9): e00377-e00319.

[36]

Tang J S, Guo M R, Chen M, et al. A link between STK signaling and capsular polysaccharide synthesis in Streptococcus suis [J]. Nature Communications, 2023, 14: 2480.

[37]

Paganelli F L, Willems R J, Jansen P, et al. Enterococcus faecium biofilm formation: identification of major autolysin AtlAEfm, associated Acm surface localization, and AtlAEfm-independent extracellular DNA Release [J]. mBio, 2013, 4(2): e00154.

[38]

Yi L, Li J P, Fan Q Y, et al. The otc gene of Streptococcus suis plays an important role in biofilm formation, adhesion, and virulence in a murine model [J]. Veterinary Microbiology, 2020, 251: 108925.

[39]

Soto Ocaña J, Friedman E S, Keenan O, et al. Metal availability shapes early life microbial ecology and community succession[J]. mBio, 2024, 15(11): e0153424.

[40]

Anderson C J, Medina C B, Barron B J, et al. Microbes exploit death-induced nutrient release by gut epithelial cells[J]. Nature, 2021, 596(7871): 262-267.

[41]

Lin L, Xu L, Lv W H, et al. An NLRP3 inflammasome-triggered cytokine storm contributes to streptococcal toxic shock-like syndrome (STSLs)[J]. PLoS Pathogens, 2019, 15(6): e1007795.

[42]

Yuan C, Hullallahli K, Huang H, et al. Zoonotic Streptococcus imports glucose to inhibit stringent response and promote growth during meningitis [J]. Nature Microbiology, 2026, 11(1): 125-141.

[43]

Berube B J, Rangel S M, Hauser A R. Pseudomonas aeruginosa: breaking down barriers [J]. Current Genetics, 2016, 62(1): 109-113.

[44]

Quan Y Y, Wang Y X, Gao S J, et al. Breaking the fortress: a mechanistic review of meningitis-causing bacteria breaching tactics in blood brain barrier[J]. Cell Communication and Signaling, 2025, 23(1): 235.

[45]

Galea I. The blood-brain barrier in systemic infection and inflammation[J]. Cellular & Molecular Immunology, 2021, 18(11): 2489-2501.

[46]

Lentini G, Midiri A, Firon A, et al. The plasminogen binding protein PbsP is required for brain invasion by hypervirulent CC17 Group B streptococci[J]. Scientific Reports, 2018, 8: 14322.

[47]

Lu Y J, Li S, Shen X D, et al. The type II histidine triad protein HtpsC facilitates invasion of epithelial cells by highly virulent Streptococcus suis serotype 2 [J]. Journal of Microbiology, 2021, 59(10): 949-957.

[48]

Kim B J, Hancock B M, Bermudez A, et al. Bacterial induction of Snail1 contributes to blood-brain barrier disruption[J]. The Journal of Clinical Investigation, 2015, 125(6): 2473-2483.

[49]

Sayoc-Becerra A, Krishnan M, Fan S J, et al. The JAK-inhibitor tofacitinib rescues human intestinal epithelial cells and colonoids from cytokine-induced barrier dysfunction[J]. Inflammatory Bowel Diseases, 2020, 26(3): 407-422.

[50]

Liu M X, Wang Q, Wu W D, et al. Glaesserella parasuis serotype 5 breaches the porcine respiratory epithelial barrier by inducing autophagy and blocking the cell membrane Claudin-1 replenishment [J]. PLoS Pathogens, 2022, 18(10): e1010912.

[51]

Gregorc U, Ivanova S, Thomas M, et al. Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important step for cell-cell detachment in apoptosis[J]. Apoptosis, 2007, 12(2): 343-354.

[52]

Xu L, Lu X, Xiao P, et al. Interleukin-17A contributed to the damage of blood-CNS barriers during Streptococcus suis meningitis [J]. Molecular Neurobiology, 2022, 59(4): 2116-2128.

[53]

Liu R, Li W Y, Meng Y, et al. The serine/threonine protein kinase of Streptococcus suis serotype 2 affects the ability of the pathogen to penetrate the blood-brain barrier [J]. Cellular Microbiology, 2018, 20(10): e12862.

[54]

Ma Z, Peng J, Yu D D, et al. A streptococcal Fic domain-containing protein disrupts blood-brain barrier integrity by activating moesin in endothelial cells[J]. PLoS Pathogens, 2019, 15(5): e1007737.

[55]

Yang Y X, Fang H W, Xie Z D, et al. Yersinia infection induces glucose depletion and AMPK-dependent inhibition of pyroptosis in mice [J]. Nature Microbiology, 2024, 9(8): 2144-2159.

[56]

Deo P, Chow S H, Han M L, et al. Mitochondrial dysfunction caused by outer membrane vesicles from Gram-negative bacteria activates intrinsic apoptosis and inflammation[J]. Nature Microbiology, 2020, 5(11): 1418-1427.

[57]

Pan F, Zhu M L, Liang Y, et al. Membrane vesicle delivery of a streptococcal M protein disrupts the blood-brain barrier by inducing autophagic endothelial cell death[J]. Proc Natl Acad Sci USA, 2023, 120(24): e2219435120.

[58]

Gao S, Wu W T, Xiao X X, et al. RfeA from Streptococcus suis serotype 2 triggers NLRP3/Caspase-1-dependent pyroptosis leading to blood-brain barrier disruption [J]. Veterinary Research, 2025, 56(1): 184.

[59]

Jiang H X, Sun Y, Li F Y, et al. Enolase of Streptococcus suis serotype 2 promotes biomolecular condensation of ribosomal protein SA for HBMECs apoptosis [J]. BMC Biology, 2024, 22(1): 33.

[60]

Russell R J, Boulet L P, Brightling C E, et al. The airway epithelium: an orchestrator of inflammation, a key structural barrier and a therapeutic target in severe asthma[J]. The European Respiratory Journal, 2024, 63(4): 2301397.

[61]

Casadevall A. Cryptococci at the brain gate: break and enter or use a Trojan horse?[J]. The Journal of Clinical Investigation, 2010, 120(5): 1389-1392.

[62]

Wang H R, Song X Y, Wang Y, et al. Interleukin 1β mediates the pathogenesis of nasal mucosal epithelial barrier dysfunction in allergic rhinitis[J]. Journal of Inflammation Research, 2024, 17.: 9071-9085.

[63]

Wang Q, Zhou H, Fan H J, et al. Coinfection with porcine circovirus type 2 (PCV2) and Streptococcus suis serotype 2 (SS2) enhances the survival of SS2 in swine tracheal epithelial cells by decreasing reactive oxygen species production [J]. Infection and Immunity, 2020, 88(11): e00520-e00537.

[64]

Bergsten H, Nizet V. The intricate pathogenicity of Group A Streptococcus: a comprehensive update [J]. Virulence, 2024, 15(1): 2412745.

[65]

Sender R, Weiss Y, Navon Y, et al. The total mass, number, and distribution of immune cells in the human body[J]. Proc Natl Acad Sci USA, 2023, 120(44): e2308511120.

[66]

Benga L, Fulde M, Neis C, et al. Polysaccharide capsule and suilysin contribute to extracellular survival of Streptococcus suis co-cultivated with primary porcine phagocytes [J]. Veterinary Microbiology, 2008, 132(1/2): 211-219.

[67]

Gao S J, Mao C L, Yuan S, et al. AI-2 quorum sensing-induced galactose metabolism activation in Streptococcus suis enhances capsular polysaccharide-associated virulence [J]. Veterinary Research, 2024, 55(1): 80.

[68]

Yang K Y, Wang Q C, Liu M X, et al. Streptococcus suis employs the Ihk/Irr-PepO axis to subvert macrophage actin polymerization: a novel antiphagocytic strategy enhancing bacterial virulence [J]. Veterinary Microbiology, 2025, 310: 110726.

[69]

Nan D Q, Rao C L, Tang Z H, et al. Burkholderia pseudomallei BipD modulates host mitophagy to evade killing [J]. Nature Communications, 2024, 15: 4740.

[70]

Lee J W, Nam H, Kim L E, et al. TLR4 (Toll-like receptor 4) activation suppresses autophagy through inhibition of FOXO3 and impairs phagocytic capacity of microglia[J]. Autophagy, 2019, 15(5): 753-770.

[71]

Lu P L, Ma D, Chen Y L, et al. L-glutamine provides acid resistance for Escherichia coli through enzymatic release of ammonia [J]. Cell Research, 2013, 23(5): 635-644.

[72]

Tong H C, Dong Y Z, Wang X H, et al. Redox-regulated adaptation of Streptococcus oligofermentans to hydrogen peroxide stress [J]. mSystems, 2020, 5(2): e00006-e00020.

[73]

Li W Y, Yin Y F, Meng Y, et al. The phosphorylation of phosphoglucosamine mutase GlmM by Ser/Thr kinase STK mediates cell wall synthesis and virulence in Streptococcus suis serotype 2 [J]. Veterinary Microbiology, 2021, 258: 109102.

[74]

Pang S Q, Qiao Z L, Xu J J, et al. Streptococcus suis AdcA interacts with factor H and inhibits C3b deposition on the bacteria to participate in complement evasion [J]. Veterinary Microbiology, 2025, 306: 110561.

[75]

Ma F, Wang G Y, Ma Z, et al. A surface protein identified from Streptococcus suis serotype 2 exhibits neutrophil-resistance via its polysaccharide capsule [J]. Microbial Pathogenesis, 2025, 199: 107270.

[76]

de Buhr N, Neumann A, Jerjomiceva N, et al. Streptococcus suis DNase SsnA contributes to degradation of neutrophil extracellular traps (NETs) and evasion of NET-mediated antimicrobial activity [J]. Microbiology, 2014, 160(Pt2): 385-395.

[77]

Emgård J, Bergsten H, McCormick J K, et al. MAIT cells are major contributors to the cytokine response in group A streptococcal toxic shock syndrome[J]. Proc Natl Acad Sci USA, 2019, 116(51): 25923-25931.

[78]

de Greeff A, Benga L, Wichgers Schreur P J, et al. Involvement of NF-kappaB and MAP-kinases in the transcriptional response of alveolar macrophages to Streptococcus suis [J]. Veterinary Microbiology, 2010, 141(1/2): 59-67.

[79]

Jiang X, Li F Y, Mei J K, et al. Brain immune cell infiltration and serum metabolomic characteristics reveal that lauric acid promotes immune cell infiltration in brain and Streptococcus suis meningitis in mice [J]. Molecular Neurobiology, 2024, 61(11): 9302-9319.

[80]

Fu Y, Jie J, Lei L, et al. Exploring the destructive synergy between IL-33 and Suilysin hemolysis on blood-brain barrier stability[J]. Microbiology Spectrum, 2024, 12(8): e0061224.

基金资助

国家重点研发计划项目(2021YFD1800400)

国家自然科学基金项目(32373018)

中国科协青年人才托举工程博士生专项计划项目(156-O-230-0000197-9)

江苏省农业科技自主创新资金项目(CX(23)1029)

江苏高校优势学科建设工程专项资金项目(PAPD)

AI Summary AI Mindmap
PDF (2539KB)

0

访问

0

被引

详细

导航
相关文章

AI思维导图

/

〈 〉