Interactions of Streptococcus suis serotype 9 with host cells and role of the capsular polysaccharide: Comparison with serotypes 2 and 14

Autoři: Jean-Philippe Auger aff001;  Servane Payen aff001;  David Roy aff001;  Audrey Dumesnil aff001;  Mariela Segura aff001;  Marcelo Gottschalk aff001
Působiště autorů: Research Group on Infectious Diseases in Production Animals (GREMIP) and Swine and Poultry Infectious Diseases Research Center (CRIPA), Department of Pathology and Microbiology, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Queb aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223864


Streptococcus suis is an important porcine bacterial pathogen and a zoonotic agent responsible for sudden death, septic shock and meningitis, of which serotype 2 is the most widespread, with serotype 14 also causing infections in humans in South-East Asia. Knowledge of its pathogenesis and virulence are almost exclusively based on these two serotypes. Though serotype 9 is responsible for the greatest number of porcine cases in Spain, the Netherlands and Germany, very little information is currently available regarding this serotype. Of the different virulence factors, the capsular polysaccharide (CPS) is required for S. suis virulence as it promotes resistance to phagocytosis and killing and masks surface components responsible for host cell activation. However, these roles have been described for serotypes 2 and 14, whose CPSs are structurally and compositionally similar, both containing sialic acid. Consequently, we evaluated herein the interactions of serotype 9 with host cells and the role of its CPS, which greatly differs from those of serotypes 2 and 14. Results demonstrated that serotype 9 adhesion to but not invasion of respiratory epithelial cells was greater than that of serotypes 2 and 14. Furthermore serotype 9 was more internalized by macrophages but equally resistant to whole blood killing. Though recognition of serotypes 2, 9 and 14 by DCs required MyD88-dependent signaling, in vitro pro-inflammatory mediator production induced by serotype 9 was much lower. In vivo, however, serotype 9 causes an exacerbated inflammatory response, which combined with persistent bacterial presence, is probably responsible for host death during the systemic infection. Though presence of the serotype 9 CPS masks surface components less efficiently than those of serotypes 2 and 14, the serotype 9 CPS remains critical for virulence as it is required for survival in blood and development of clinical disease, and this regardless of its unique composition and structure.

Klíčová slova:

Blood – Host cells – Mouse models – Mutant strains – Phagocytosis – Toll-like receptors – Streptococcus suis – Sialic acids


1. Gottschalk M, Xu J, Calzas C, Segura M. Streptococcus suis: a new emerging or an old neglected zoonotic pathogen? Future Microbiol. 2010;5: 371–391. doi: 10.2217/fmb.10.2 20210549

2. Goyette-Desjardins G, Auger J-P, 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. Emerg Microbes Infect. 2014;3: e45. doi: 10.1038/emi.2014.45 26038745

3. Roy D, Auger JP, Segura M, Fittipaldi N, Takamatsu D, Okura M, et al. Role of the capsular polysaccharide as a virulence factor for Streptococcus suis serotype 14. Can J Vet Res. 2015;79: 141–146. 25852230

4. Kerdsin A, Oishi K, Sripakdee S, Boonkerd N, Polwichai P, Nakamura S, et al. Clonal dissemination of human isolates of Streptococcus suis serotype 14 in Thailand. J Med Microbiol. 2009;58: 1508–1513. doi: 10.1099/jmm.0.013656-0 19661209

5. Fittipaldi N, Segura M, Grenier D, Gottschalk M. Virulence factors involved in the pathogenesis of the infection caused by the swine pathogen and zoonotic agent Streptococcus suis. Future Microbiol. 2012;7: 259–279. doi: 10.2217/fmb.11.149 22324994

6. Segura M, Calzas C, Grenier D, Gottschalk M. Initial steps of the pathogenesis of the infection caused by Streptococcus suis: fighting against nonspecific defenses. FEBS Lett. 2016;590: 3772–3799. doi: 10.1002/1873-3468.12364 27539145

7. Zhu H, Huang D, Zhang W, Wu Z, Lu Y, Jia H, et al. The novel virulence-related gene stp of Streptococcus suis serotype 9 strain contributes to a significant reduction in mouse mortality. Microb Pathog. 2011;51: 442–453. doi: 10.1016/j.micpath.2011.08.002 21924346

8. Gottschalk M, Lacouture S. Canada: Distribution of Streptococcus suis (from 2012 to 2014) and Actinobacillus pleuropneumoniae (from 2011 to 2014) serotypes isolated from diseased pigs. Can Vet J. 2015;56: 1093–1094. 26483588

9. Kerdsin A, Hatrongjit R, Gottschalk M, Takeuchi D, Hamada S, Akeda Y, et al. Emergence of Streptococcus suis serotype 9 infection in humans. J Microbiol Immunol Infect. 2015;15: 1–2.

10. Ferrando ML, de Greeff A, van Rooijen WJ, Stockhofe-Zurwieden N, Nielsen J, Wichgers Schreur PJ, et al. Host-pathogen interaction at the intestinal mucosa correlates with zoonotic potential of Streptococcus suis. J Infect Dis. 2015;212: 95–105. doi: 10.1093/infdis/jiu813 25525050

11. Auger J-P, Boa A-C, Segura M, Gottschalk M. Antigen I/II participates in the interactions of Streptococcus suis serotype 9 with phagocytes and the development of systemic disease. Front Cell Infect Microbiol. 2019;9.

12. Chuzeville S, Auger JP, Dumesnil A, Roy D, Lacouture S, Fittipaldi N, et al. Serotype-specific role of antigen I/II in the initial steps of the pathogenesis of the infection caused by Streptococcus suis. Vet Res. 2017;48: 39. doi: 10.1186/s13567-017-0443-4 28705175

13. Chabot-Roy G, Willson P, Segura M, Lacouture S, Gottschalk M. Phagocytosis and killing of Streptococcus suis by porcine neutrophils. Microb Pathog. 2006;41: 21–32. doi: 10.1016/j.micpath.2006.04.001 16714092

14. Benga L, Fulde M, Neis C, Goethe R, Valentin-Weigand P. Polysaccharide capsule and suilysin contribute to extracellular survival of Streptococcus suis co-cultivated with primary porcine phagocytes. Vet Microbiol. 2008;132: 211–219. doi: 10.1016/j.vetmic.2008.05.005 18565698

15. Segura M, Gottschalk M, Olivier M. Encapsulated Streptococcus suis inhibits activation of signaling pathways involved in phagocytosis. Infect Immun. 2004;72: 5322–5330. doi: 10.1128/IAI.72.9.5322-5330.2004 15322029

16. Segura MA, Cleroux P, Gottschalk M. Streptococcus suis and Group B Streptococcus differ in their interactions with murine macrophages. FEMS Immunol Med Microbiol. 1998;21: 189–195. doi: 10.1111/j.1574-695X.1998.tb01165.x 9718208

17. Lecours MP, Gottschalk M, Houde M, Lemire P, Fittipaldi N, Segura M. Critical role for Streptococcus suis cell wall modifications and suilysin in resistance to complement-dependent killing by dendritic cells. J Infect Dis. 2011;204: 919–929. doi: 10.1093/infdis/jir415 21849289

18. Auger JP, Dolbec D, Roy D, Segura M, Gottschalk M. Role of the Streptococcus suis serotype 2 capsular polysaccharide in the interactions with dendritic cells is strain-dependent but remains critical for virulence. PLoS One. 2018;13: e0200453. doi: 10.1371/journal.pone.0200453 30001363

19. Graveline R, Segura M, Radzioch D, Gottschalk M. TLR2-dependent recognition of Streptococcus suis is modulated by the presence of capsular polysaccharide which modifies macrophage responsiveness. Int Immunol. 2007;19: 375–389. doi: 10.1093/intimm/dxm003 17307800

20. Lecours MP, Segura M, Fittipaldi N, Rivest S, Gottschalk M. Immune receptors involved in Streptococcus suis recognition by dendritic cells. PLoS One. 2012;7: e44746. doi: 10.1371/journal.pone.0044746 22984550

21. Lecours MP, Fittipaldi N, Takamatsu D, Okura M, Segura M, Goyette-Desjardins G, et al. Sialylation of Streptococcus suis serotype 2 is essential for capsule expression but is not responsible for the main capsular epitope. Microbes and infection / Institut Pasteur. 2012;14: 941–950.

22. Smith HE, Damman M, van der Velde J, Wagenaar F, Wisselink HJ, Stockhofe-Zurwieden N, et al. Identification and characterization of the cps locus of Streptococcus suis serotype 2: the capsule protects against phagocytosis and is an important virulence factor. Infect Immun. 1999;67: 1750–1756. 10085014

23. Auger JP, Meekhanon N, Okura M, Osaki M, Gottschalk M, Sekizaki T, et al. Streptococcus suis serotype 2 capsule in vivo. Emerg Infect Dis. 2016;22: 1793–1796. doi: 10.3201/eid2210.151640 27648583

24. Roy D, Athey TBT, Auger JP, Goyette-Desjardins G, Van Calsteren MR, Takamatsu D, et al. A single amino acid polymorphism in the glycosyltransferase CpsK defines four Streptococcus suis serotypes. Sci Rep. 2017;7: 4066. doi: 10.1038/s41598-017-04403-3 28642597

25. Van Calsteren MR, Gagnon F, Calzas C, Goyette-Desjardins G, Okura M, Takamatsu D, et al. Structure determination of Streptococcus suis serotype 14 capsular polysaccharide. Biochem Cell Biol. 2013;91: 49–58. doi: 10.1139/bcb-2012-0036 23527632

26. Van Calsteren MR, Gagnon F, Lacouture S, Fittipaldi N, Gottschalk M. Structure determination of Streptococcus suis serotype 2 capsular polysaccharide. Biochem Cell Biol. 2010;88: 513–525. doi: 10.1139/o09-170 20555393

27. Van Calsteren MR, Goyette-Desjardins G, Gagnon F, Okura M, Takamatsu D, Roy R, et al. Explaining the serological characteristics of Streptococcus suis serotypes 1 and 1/2 from their capsular polysaccharide structure and biosynthesis. J Biol Chem. 2016.

28. Segura M. Fisher scientific award lecture—the capsular polysaccharides of Group B Streptococcus and Streptococcus suis differently modulate bacterial interactions with dendritic cells. Can J Microbiol. 2012;58: 249–260. doi: 10.1139/w2012-003 22356626

29. Weiman S, Dahesh S, Carlin AF, Varki A, Nizet V, Lewis AL. Genetic and biochemical modulation of sialic acid O-acetylation on Group B Streptococcus: phenotypic and functional impact. Glycobiology. 2009;19: 1204–1213. doi: 10.1093/glycob/cwp111 19643844

30. Weiman S, Uchiyama S, Lin F-YC, Chaffin D, Varki A, Nizet V, et al. O-acetylation of sialic acid on Group B Streptococcus inhibits neutrophil suppression and virulence. The Biochemical journal. 2010;428: 163–168. doi: 10.1042/BJ20100232 20334627

31. Roy D, Takamatsu D, Okura M, Goyette-Desjardins G, Van Calsteren MR, Dumesnil A, et al. Capsular sialyltransferase specificity mediates different phenotypes in Streptococcus suis and Group B Streptococcus. Frontiers in microbiology. 2018;9: 545. doi: 10.3389/fmicb.2018.00545 29666608

32. Lakkitjaroen N, Takamatsu D, Okura M, Sato M, Osaki M, Sekizaki T. Capsule loss or death: the position of mutations among capsule genes sways the destiny of Streptococcus suis. FEMS Microbiol Lett. 2014;354: 46–54. doi: 10.1111/1574-6968.12428 24654559

33. Vinogradov E, Goyette-Desjardins G, Okura M, Takamatsu D, Gottschalk M, Segura M. Structure determination of Streptococcus suis serotype 9 capsular polysaccharide and assignment of functions of the cps locus genes involved in its biosynthesis. Carbohydr Res. 2016;433: 25–30. doi: 10.1016/j.carres.2016.07.005 27423880

34. Zheng H, Du P, Qiu X, Kerdsin A, Roy D, Bai X, et al. Genomic comparisons of Streptococcus suis serotype 9 strains recovered from diseased pigs in Spain and Canada. Vet Res. 2018;49: 1. doi: 10.1186/s13567-017-0498-2 29316972

35. Auger J-P, Santinón A, Roy D, Mossman K, Xu J, Segura M, et al. Type I interferon induced by Streptococcus suis serotype 2 is strain-dependent and may be beneficial for host survival. Front Immunol. 2017;8.

36. Auger J-P, Fittipaldi N, Benoit-Biancamano M-O, Segura M, Gottschalk M. Virulence studies of different sequence types and geographical origins of Streptococcus suis serotype 2 in a mouse model of infection. Pathogens. 2016;5: 48.

37. Dominguez-Punaro M, Segura M, Plante MM, Lacouture S, Rivest S, Gottschalk M. Streptococcus suis serotype 2, an important swine and human pathogen, induces strong systemic and cerebral inflammatory responses in a mouse model of infection. J Immunol. 2007;179: 1842–1854. doi: 10.4049/jimmunol.179.3.1842 17641051

38. Dominguez-Punaro M, Segura M, Radzioch D, Rivest S, Gottschalk M. Comparison of the susceptibilities of C57BL/6 and A/J mouse strains to Streptococcus suis serotype 2 infection. Infect Immun. 2008;76: 3901–3910. doi: 10.1128/IAI.00350-08 18573893

39. Slater JD, Allen AG, May JP, Bolitho S, Lindsay H, Maskell DJ. Mutagenesis of Streptococcus equi and Streptococcus suis by transposon Tn917. Vet Microbiol. 2003;93: 197–206. doi: 10.1016/s0378-1135(03)00030-0 12695044

40. Gottschalk M, Higgins R, Jacques M, Mittal KR, Henrichsen J. Description of 14 new capsular types of Streptococcus suis. J Clin Microbiol. 1989;27: 2633–2636. 2480359

41. Takamatsu D, Osaki M, Sekizaki T. Thermosensitive suicide vectors for gene replacement in Streptococcus suis. Plasmid. 2001;46: 140–148. doi: 10.1006/plas.2001.1532 11591139

42. Warrens AN, Jones MD, Lechler RI. Splicing by overlap extension by PCR using asymmetric amplification: an improved technique for the generation of hybrid proteins of immunological interest. Gene. 1997;186: 29–35. doi: 10.1016/s0378-1119(96)00674-9 9047341

43. Auger J-P, Chuzeville S, Roy D, Mathieu-Denoncourt A, Xu J, Grenier D, et al. The bias of experimental design, including strain background, in the determination of critical Streptococcus suis serotype 2 virulence factors. PLoS One. 2017;12: e0181920. doi: 10.1371/journal.pone.0181920 28753679

44. Jacques M, Gottschalk M, Foiry B, Higgins R. Ultrastructural study of surface components of Streptococcus suis. J Bacteriol. 1990;172: 2833–2838. doi: 10.1128/jb.172.6.2833-2838.1990 1971617

45. Wang Y, Gagnon CA, Savard C, Music N, Srednik M, Segura M, et al. Capsular sialic acid of Streptococcus suis serotype 2 binds to swine influenza virus and enhances bacterial interactions with virus-infected tracheal epithelial cells. Infect Immun. 2013;81: 4498–4508. doi: 10.1128/IAI.00818-13 24082069

46. Segura M, Su Z, Piccirillo C, Stevenson MM. Impairment of dendritic cell function by excretory-secretory products: a potential mechanism for nematode-induced immunosuppression. Eur J Immunol. 2007;37: 1887–1904. doi: 10.1002/eji.200636553 17563917

47. Lavagna A, Auger JP, Dumesnil A, Roy D, Girardin SE, Gisch N, et al. Interleukin-1 signaling induced by Streptococcus suis serotype 2 is strain-dependent and contributes to bacterial clearance and inflammation during systemic disease in a mouse model of infection. Vet Res. 2019: Forthcoming.

48. Lachance C, Gottschalk M, Gerber PP, Lemire P, Xu J, Segura M. Exacerbated type II interferon response drives hypervirulence and toxic shock by an emergent epidemic strain of Streptococcus suis. Infect Immun. 2013;81: 1928–1939. doi: 10.1128/IAI.01317-12 23509145

49. Feng Y, Cao M, Shi J, Zhang H, Hu D, Zhu J, et al. Attenuation of Streptococcus suis virulence by the alteration of bacterial surface architecture. Sci Rep. 2012;2: 710. doi: 10.1038/srep00710 23050094

50. Letendre C, Auger JP, Lemire P, Galbas T, Gottschalk M, Thibodeau J, et al. Streptococcus suis serotype 2 infection impairs interleukin-12 production and the MHC-II-restricted antigen presentation capacity of dendritic cells. Front Immunol. 2018;9: 1199. doi: 10.3389/fimmu.2018.01199 29899744

51. Bi L, Pian Y, Chen S, Ren Z, Liu P, Lv Q, et al. Toll-like receptor 4 confers inflammatory response to suilysin. Front Microbiol. 2015;6: 644. doi: 10.3389/fmicb.2015.00644 26167160

52. King SJ, Heath PJ, Luque I, Tarradas C, Dowson CG, Whatmore AM. Distribution and genetic diversity of suilysin in Streptococcus suis isolated from different diseases of pigs and characterization of the genetic basis of suilysin absence. Infect Immun. 2001;69: 7572–7582. doi: 10.1128/IAI.69.12.7572-7582.2001 11705935

53. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4: 499–511. doi: 10.1038/nri1391 15229469

54. Lalonde M, Segura M, Lacouture S, Gottschalk M. Interactions between Streptococcus suis serotype 2 and different epithelial cell lines. Microbiology. 2000;146: 1913–1921. doi: 10.1099/00221287-146-8-1913 10931895

55. Auger JP, Christodoulides M, Segura M, Xu J, Gottschalk M. Interactions of Streptococcus suis serotype 2 with human meningeal cells and astrocytes. BMC Res Notes. 2015;8: 607. doi: 10.1186/s13104-015-1581-2 26502903

56. Benga L, Goethe R, Rohde M, Valentin-Weigand P. Non-encapsulated strains reveal novel insights in invasion and survival of Streptococcus suis in epithelial cells. Cell Microbiol. 2004;6: 867–881. doi: 10.1111/j.1462-5822.2004.00409.x 15272867

57. Roy D, Fittipaldi N, Dumesnil A, Lacouture S, Gottschalk M. The protective protein Sao (surface antigen one) is not a critical virulence factor for Streptococcus suis serotype 2. Microb Pathog. 2014;67–68: 31–35. doi: 10.1016/j.micpath.2014.02.002 24530923

58. Segura M, Fittipaldi N, Calzas C, Gottschalk M. Critical Streptococcus suis virulence factors: Are they all really critical? Trends Microbiol. 2017;25: 585–599. doi: 10.1016/j.tim.2017.02.005 28274524

59. Meijerink M, Ferrando ML, Lammers G, Taverne N, Smith HE, Wells JM. Immunomodulatory effects of Streptococcus suis capsule type on human dendritic cell responses, phagocytosis and intracellular survival. PLoS One. 2012;7: e35849. doi: 10.1371/journal.pone.0035849 22558240

60. Severi E, Hood DW, Thomas GH. Sialic acid utilization by bacterial pathogens. Microbiology. 2007;153: 2817–2822. doi: 10.1099/mic.0.2007/009480-0 17768226

61. Vimr E, Lichtensteiger C. To sialylate, or not to sialylate: that is the question. Trends Microbiol. 2002;10: 254–257. doi: 10.1016/s0966-842x(02)02361-2 12088651

62. Dale DC, Boxer L, Liles WC. The phagocytes: neutrophils and monocytes. Blood. 2008;112: 935–945. doi: 10.1182/blood-2007-12-077917 18684880

63. Zhang Y, Ding D, Liu M, Yang X, Zong B, Wang X, et al. Effect of the glycosyltransferases on the capsular polysaccharide synthesis of Streptococcus suis serotype 2. Microbiol Res. 2016;185: 45–54. doi: 10.1016/j.micres.2016.02.002 26946377

64. Gottschalk M. Streptococcosis. In: Zimmerman JJ, Ramirez A, Schwartz KJ, Stevenson GW, editors. Diseases of swine. 10th ed. Ames, USA: Wiley-Blackwell Publishing; 2012. p. 841–855.

65. Lecours MP, Segura M, Lachance C, Mussa T, Surprenant C, Montoya M, et al. Characterization of porcine dendritic cell response to Streptococcus suis. Vet Res. 2011;42: 72. doi: 10.1186/1297-9716-42-72 21635729

66. Wichgers Schreur PJ, Rebel JM, Smits MA, van Putten JP, Smith HE. Differential activation of the Toll-like receptor 2/6 complex by lipoproteins of Streptococcus suis serotypes 2 and 9. Vet Microbiol. 2010;143: 363–370. doi: 10.1016/j.vetmic.2009.12.010 20044219

67. Lacy P, Stow JL. Cytokine release from innate immune cells: association with diverse membrane trafficking pathways. Blood. 2011;118: 9–18. doi: 10.1182/blood-2010-08-265892 21562044

Článek vyšel v časopise


2019 Číslo 10

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Zvyšte si kvalifikaci online z pohodlí domova

Léčba bolesti v ordinaci praktického lékaře
nový kurz
Autoři: MUDr. PhDr. Zdeňka Nováková, Ph.D.

Revmatoidní artritida: včas a k cíli
Autoři: MUDr. Heřman Mann

Jistoty a nástrahy antikoagulační léčby aneb kardiolog - neurolog - farmakolog - nefrolog - právník diskutují
Autoři: doc. MUDr. Štěpán Havránek, Ph.D., prof. MUDr. Roman Herzig, Ph.D., doc. MUDr. Karel Urbánek, Ph.D., prim. MUDr. Jan Vachek, MUDr. et Mgr. Jolana Těšínová, Ph.D.

Léčba akutní pooperační bolesti
Autoři: doc. MUDr. Jiří Málek, CSc.

Nové antipsychotikum kariprazin v léčbě schizofrenie
Autoři: prof. MUDr. Cyril Höschl, DrSc., FRCPsych.

Všechny kurzy
Kurzy Doporučená témata Časopisy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se