Biological Activities of Suilysin: Role in Streptococcus Suis Pathogenesis

References

• Staats JJ, Feder I, Okwumabua O, Chengappa MM. Streptococcus suis: past and present. Vet. Res. Commun. 21 (6 ), 381 – 407 (1997).
   PubMed Web of Science ®Google Scholar
• Chanter N, Jones PW, Alexander TJ. Meningitis in pigs caused by Streptococcus suis – a speculative review. Vet. Microbiol. 36 (1 ), 39 – 55 (1993).
   PubMed Web of Science ®Google Scholar
• Seitz M, Beineke A, Singpiel A et al. Role of capsule and suilysin in mucosal infection of complement-deficient mice with Streptococcus suis. Infect. Immun. 82 (6 ), 2460 – 2471 (2014).
   PubMed Web of Science ®Google Scholar
• Gottschalk M, Segura M, Xu J. Streptococcus suis infections in humans: the Chinese experience and the situation in North America. Anim. Health Res. Rev. 8 (1 ), 29 – 45 (2007).
   PubMedGoogle Scholar
• Arends JP, Zanen HC. Meningitis caused by Streptococcus-suis in humans. Rev. Infect. Dis. 10 (1 ), 131 – 137 (1988).
   PubMedGoogle Scholar
• Gottschalk M, Xu JG, Calzas C, Segura M. Streptococcus suis: a new emerging or an old neglected zoonotic pathogen? Future Microbiol. 5 (3 ), 371 – 391 (2010).
   PubMed Web of Science ®Google Scholar
• Gottschalk M, Higgins R, Quessy S. Dilemma of the virulence of Streptococcus suis strains. J. Clin. Microbiol. 37 (12 ), 4202 – 4203 (1999).
   PubMed Web of Science ®Google Scholar
• 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. 69 (12 ), 7572 – 7582 (2001).
   PubMed Web of Science ®Google Scholar
• 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. Emerg. Microbes Infect. 3 (6 ), e45 (2014).
   PubMed Web of Science ®Google Scholar
• Mai NT, Hoa NT, Nga TV et al. Streptococcus suis meningitis in adults in Vietnam. Clin. Infect. Dis. 46 (5 ), 659 – 667 (2008).
   PubMed Web of Science ®Google Scholar
• Baums CG, Valentin-Weigand P. Surface-associated and secreted factors of Streptococcus suis in epidemiology, pathogenesis and vaccine development. Anim. Health Res. Rev. 10 (1 ), 65 – 83 (2009).
   PubMedGoogle Scholar
• 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. 67 (4 ), 1750 – 1756 (1999).
   PubMed Web of Science ®Google Scholar
• Jacobs AaC, Loeffen PLW, Vandenberg AJG, Storm PK. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus-suis. Infect. Immun. 62 (5 ), 1742 – 1748 (1994).
   PubMed Web of Science ®Google Scholar
• Jacobs AA, Van Den Berg AJ, Baars JC, Nielsen B, Johannsen LW. Production of suilysin, the thiol-activated haemolysin of Streptococcus suis by field isolates from diseased pigs. Vet. Rec. 137 (12 ), 295 – 296 (1995).
   PubMed Web of Science ®Google Scholar
• Vecht U, Wisselink HJ, Jellema ML, Smith HE. Identification of two proteins associated with virulence of Streptococcus suis type 2. Infect. Immun. 59 (9 ), 3156 – 3162 (1991).
   PubMed Web of Science ®Google Scholar
• Brassard J, Gottschalk M, Quessy S. Cloning and purification of the Streptococcus suis serotype 2 glyceraldehyde-3-phosphate dehydrogenase and its involvement as an adhesin. Vet. Microbiol. 102 (1 ), 87 – 94 (2004).
   PubMed Web of Science ®Google Scholar
• Smith HE, Vecht U, Gielkens ALJ, Smits MA. Cloning and nucleotide-sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus-suis type-2. Infect. Immun. 60 (6 ), 2361 – 2367 (1992).
   PubMed Web of Science ®Google Scholar
• De Greeff A, Buys H, Verhaar R, Dijkstra J, Van Alphen L, Smith HE. Contribution of fibronectin-binding protein to pathogenesis of Streptococcus suis serotype 2. Infect. Immun. 70 (3 ), 1319 – 1325 (2002).
   PubMed Web of Science ®Google Scholar
• King SJ, Allen AG, Maskell DJ, Dowson CG, Whatmore AM. Distribution, genetic diversity, and variable expression of the gene encoding hyaluronate lyase within the Streptococcus suis population. J. Bacteriol. 186 (14 ), 4740 – 4747 (2004).
   PubMed Web of Science ®Google Scholar
• 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. 7 (2 ), 259 – 279 (2012).
   PubMed Web of Science ®Google Scholar
• Feng Y, Zhang H, Wu Z et al. Streptococcus suis infection: an emerging/reemerging challenge of bacterial infectious diseases? Virulence 5 (4 ), 477 – 497 (2014).
   PubMed Web of Science ®Google Scholar
• 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. Clin. Microbiol. 39 (2 ), 445 – 453 (2001).
   PubMed Web of Science ®Google Scholar
• Gottschalk M, Segura M. The pathogenesis of the meningitis caused by Streptococcus suis: the unresolved questions. Vet. Microbiol. 76 (3 ), 259 – 272 (2000).
   PubMed Web of Science ®Google Scholar
• Segers RP, Kenter T, De Haan LA, Jacobs AA. Characterisation of the gene encoding suilysin from Streptococcus suis and expression in field strains. FEMS Microbiol. Lett. 167 (2 ), 255 – 261 (1998).
   PubMed Web of Science ®Google Scholar
• Allen AG, Bolitho S, Lindsay H et al. Generation and characterization of a defined mutant of Streptococcus suis lacking suilysin. Infect. Immun. 69 (4 ), 2732 – 2735 (2001).
   PubMed Web of Science ®Google Scholar
• Lun S, Perez-Casal J, Connor W, Willson PJ. Role of suilysin in pathogenesis of Streptococcus suis capsular serotype 2. Microb. Pathog. 34 (1 ), 27 – 37 (2003).
   PubMed Web of Science ®Google Scholar
• He Z, Pian Y, Ren Z et al. Increased production of suilysin contributes to invasive infection of the Streptococcus suis strain 05ZYH33. Mol. Med. Rep. 10 (6 ), 2819 – 2826 (2014).
   PubMed Web of Science ®Google Scholar
• De Greeff A, Wisselink HJ, De Bree FM et al. Genetic diversity of Streptococcus suis isolates as determined by comparative genome hybridization. BMC Microbiol. 11, 161 (2011).
   PubMed Web of Science ®Google Scholar
• Barnett TC, Cole JN, Rivera-Hernandez T et al. Streptococcal toxins: role in pathogenesis and disease. Cell Microbiol. 17 (12 ), 1721 – 1741 (2015).
   PubMed Web of Science ®Google Scholar
• Berry AM, Yother J, Briles DE, Hansman D, Paton JC. Reduced virulence of a defined pneumolysin-negative mutant of Streptococcus pneumonia. Infect. Immun. 57 (7 ), 2037 – 2042 (1989).
   PubMed Web of Science ®Google Scholar
• Kadioglu A, Gingles NA, Grattan K, Kerr A, Mitchell TJ, Andrew PW. Host cellular immune response to pneumococcal lung infection in mice. Infect. Immun. 68 (2 ), 492 – 501 (2000).
   PubMed Web of Science ®Google Scholar
• Reiss A, Braun JS, Jager K et al. Bacterial pore-forming cytolysins induce neuronal damage in a rat model of neonatal meningitis. J. Infect. Dis. 203 (3 ), 393 – 400 (2011).
   PubMed Web of Science ®Google Scholar
• Ring A, Braun JS, Pohl J, Nizet V, Stremmel W, Shenep JL. Group B streptococcal beta-hemolysin induces mortality and liver injury in experimental sepsis. J. Infect. Dis. 185 (12 ), 1745 – 1753 (2002).
   PubMed Web of Science ®Google Scholar
• Doran KS, Liu GY, Nizet V. Group B streptococcal beta-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis. J. Clin. Invest. 112 (5 ), 736 – 744 (2003).
   PubMed Web of Science ®Google Scholar
• Liu GY, Doran KS, Lawrence T et al. Sword and shield: linked group B streptococcal beta-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense. Proc. Natl Acad. Sci. USA 101 (40 ), 14491 – 14496 (2004).
   PubMed Web of Science ®Google Scholar
• Gilbert RJC, Mikelj M, Dalla Serra M, Froelich CJ, Anderluh G. Effects of MACPF/CDC proteins on lipid membranes. Cell Mol. Life Sci. 70 (12 ), 2083 – 2098 (2013).
   PubMed Web of Science ®Google Scholar
• Tweten RK. Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins. Infect. Immun. 73 (10 ), 6199 – 6209 (2005).
   PubMed Web of Science ®Google Scholar
• Hotze EM, Tweten RK. Membrane assembly of the cholesterol-dependent cytolysin pore complex. Biochim. Biophys. Acta 1818 (4 ), 1028 – 1038 (2012).
   PubMed Web of Science ®Google Scholar
• Sonnen AFP, Plitzko JM, Gilbert RJC. Incomplete pneumolysin oligomers form membrane pores. Open Biol. 4 (4 ), 140044 (2014).
   PubMed Web of Science ®Google Scholar
• Rampersaud R, Planet PJ, Randis TM et al. Inerolysin, a cholesterol-dependent cytolysin produced by Lactobacillus iners. J. Bacteriol. 193 (5 ), 1034 – 1041 (2011).
   PubMed Web of Science ®Google Scholar
• Gelber SE, Aguilar JL, Lewis KL, Ratner AJ. Functional and phylogenetic characterization of Vaginolysin, the human-specific cytolysin from Gardnerella vaginalis. J. Bacteriol. 190 (11 ), 3896 – 3903 (2008).
   PubMed Web of Science ®Google Scholar
• Walker JA, Allen RL, Falmagne P, Johnson MK, Boulnois GJ. Molecular cloning, characterization, and complete nucleotide sequence of the gene for pneumolysin, the sulfhydryl-activated toxin of Streptococcus pneumonia. Infect. Immun. 55 (5 ), 1184 – 1189 (1987).
   PubMed Web of Science ®Google Scholar
• Cassidy SK, O'riordan MX. More than a pore: the cellular response to cholesterol-dependent cytolysins. Toxins (Basel) 5 (4 ), 618 – 636 (2013).
   PubMed Web of Science ®Google Scholar
• Suarez-Alvarez B, Garcia-Suarez Mdel M, Mendez FJ, De Los Toyos JR. Characterisation of mouse monoclonal antibodies for pneumolysin: fine epitope mapping and V gene usage. Immunol. Lett. 88 (3 ), 227 – 239 (2003).
   PubMed Web of Science ®Google Scholar
• Rossjohn J, Feil SC, Mckinstry WJ, Tweten RK, Parker MW. Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its membrane form. Cell 89 (5 ), 685 – 692 (1997).
   PubMed Web of Science ®Google Scholar
• Xu LF, Huang B, Du HM et al. Crystal structure of cytotoxin protein suilysin from Streptococcus suis. Protein Cell 1 (1 ), 96 – 105 (2010).
   PubMed Web of Science ®Google Scholar
• Weis S, Palmer M. Streptolysin O: the C-terminal, tryptophan-rich domain carries functional sites for both membrane binding and self-interaction but not for stable oligomerization. Biochim. Biophys. Acta 1510 (1 ), 292 – 299 (2001).
   PubMed Web of Science ®Google Scholar
• Feldman C, Mitchell TJ, Andrew PW et al. The effect of Streptococcus pneumoniae pneumolysin on human respiratory epithelium in vitro. Microb. Pathog. 9 (4 ), 275 – 284 (1990).
   PubMed Web of Science ®Google Scholar
• Chiarot E, Faralla C, Chiappini N et al. Targeted amino acid substitutions impair streptolysin O toxicity and group A Streptococcus virulence. mBio 4 (1 ), e00387 – e00312 (2013).
   PubMed Web of Science ®Google Scholar
• Seitz M, Baums CG, Neis C et al. Subcytolytic effects of suilysin on interaction of Streptococcus suis with epithelial cells. Vet. Microbiol. 167 (3 ), 584 – 591 (2013).
   PubMed Web of Science ®Google Scholar
• Polekhina G, Giddings KS, Tweten RK, Parker MW. Crystallization and preliminary x-ray analysis of the human-specific toxin intermedilysin. Acta Crystallogr. D Biol. Crystallogr. 60 (Pt 2 ), 347 – 349 (2004).
   PubMedGoogle Scholar
• Sekino-Suzuki N, Nakamura M, Mitsui KI, Ohno-Iwashita Y. Contribution of individual tryptophan residues to the structure and activity of theta-toxin (perfringolysin O), a cholesterol-binding cytolysin. Eur. J. Biochem. 241 (3 ), 941 – 947 (1996).
   PubMedGoogle Scholar
• Xu CJ, Yuan XL, Pan Z et al. Mechanism of action of isothiocyanates: the induction of ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2. Mol. Cancer Ther. 5 (8 ), 1918 – 1926 (2006).
   PubMed Web of Science ®Google Scholar
• Ohkura K, Nagamune H, Kourai H. Structural analysis of human specific cytolysin intermedilysin aiming application to cancer immunotherapy. Anticancer Res. 24 (5C ), 3343 – 3353 (2004).
   PubMed Web of Science ®Google Scholar
• Billington SJ, Jost BH, Cuevas WA, Bright KR, Songer JG. The Arcanobacterium (Actinomyces) pyogenes hemolysin, pyolysin, is a novel member of the thiol-activated cytolysin family. J. Bacteriol. 179 (19 ), 6100 – 6106 (1997).
   PubMed Web of Science ®Google Scholar
• Michel E, Reich KA, Favier R, Berche P, Cossart P. Attenuated mutants of the intracellular bacterium Listeria monocytogenes obtained by single amino acid substitutions in listeriolysin O. Mol. Microbiol. 4 (12 ), 2167 – 2178 (1990).
   PubMed Web of Science ®Google Scholar
• Pinkney M, Beachey E, Kehoe M. The thiol-activated toxin streptolysin O does not require a thiol group for cytolytic activity. Infect. Immun. 57 (8 ), 2553 – 2558 (1989).
   PubMed Web of Science ®Google Scholar
• Saunders FK, Mitchell TJ, Walker JA, Andrew PW, Boulnois GJ. Pneumolysin, the thiol-activated toxin of Streptococcus pneumoniae does not require a thiol group for in vitro activity. Infect. Immun. 57 (8 ), 2547 – 2552 (1989).
   PubMed Web of Science ®Google Scholar
• Stachowiak R, Wisniewski J, Osinska O, Bielecki J. Contribution of cysteine residue to the properties of Listeria monocytogenes listeriolysin O. Can. J. Microbiol. 55 (10 ), 1153 – 1159 (2009).
   PubMed Web of Science ®Google Scholar
• Rossjohn J, Gilbert RJ, Crane D et al. The molecular mechanism of pneumolysin, a virulence factor from Streptococcus pneumonia. J. Mol. Biol. 284 (2 ), 449 – 461 (1998).
   PubMed Web of Science ®Google Scholar
• Rossjohn J, Polekhina G, Feil SC, Morton CJ, Tweten RK, Parker MW. Structures of perfringolysin O suggest a pathway for activation of cholesterol-dependent cytolysins. J. Mol. Biol. 367 (5 ), 1227 – 1236 (2007).
   PubMed Web of Science ®Google Scholar
• Leung C, Dudkina NV, Lukoyanova N et al. Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin. Elife 3, e04247 (2014).
   Web of Science ®Google Scholar
• Ramachandran R, Tweten RK, Johnson AE. Membrane-dependent conformational changes initiate cholesterol-dependent cytolysin oligomerization and intersubunit beta-strand alignment. Nat. Struct. Mol. Biol. 11 (8 ), 697 – 705 (2004).
   PubMed Web of Science ®Google Scholar
• Chen C, Tang J, Dong W et al. A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates. PLoS One 2 (3 ), e315 (2007).
   PubMed Web of Science ®Google Scholar
• Zheng JX, Li Y, Zhang H, Fan HJ, Lu CP. Identification and characterization of a novel hemolysis-related gene in Streptococcus suis serotype 2. PLoS One 8 (9 ), e74674 (2013).
   PubMed Web of Science ®Google Scholar
• Nakayama T, Ezoe K. Heat incubation inactivates streptococcal exotoxins and recombinant cholesterol-dependent cytolysins: suilysin, pneumolysin and streptolysin O. Curr. Microbiol. 69 (5 ), 690 – 698 (2014).
   PubMed Web of Science ®Google Scholar
• Gottschalk MG, Lacouture S, Dubreuil JD. Characterization of Streptococcus suis capsular type 2 haemolysin. Microbiology 141 (Pt 1 ), 189 – 195 (1995).
   PubMedGoogle Scholar
• Lalonde M, Segura M, Lacouture S, Gottschalk M. Interactions between Streptococcus suis serotype 2 and different epithelial cell lines. Microbiology 146, 1913 – 1921 (2000).
   PubMed Web of Science ®Google Scholar
• Norton PM, Rolph C, Ward PN, Bentley RW, Leigh JA. Epithelial invasion and cell lysis by virulent strains of Streptococcus suis is enhanced by the presence of suilysin. FEMS Immunol. Med. Microbiol. 26 (1 ), 25 – 35 (1999).
   PubMedGoogle Scholar
• Vadeboncoeur N, Segura M, Al-Numani D, Vanier G, Gottschalk M. Pro-inflammatory cytokine and chemokine release by human brain microvascular endothelial cells stimulated by Streptococcus suis serotype 2. FEMS Immunol. Med. Microbiol. 35 (1 ), 49 – 58 (2003).
   PubMedGoogle Scholar
• Vanier G, Segura M, Friedl P, Lacouture S, Gottschalk M. Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2. Infect. Immun. 72 (3 ), 1441 – 1449 (2004).
   PubMed Web of Science ®Google Scholar
• Vanier G, Segura M, Gottschalk M. Characterization of the invasion of porcine endothelial cells by Streptococcus suis serotype 2. Can. J. Vet. Res. 71 (2 ), 81 – 89 (2007).
   PubMed Web of Science ®Google Scholar
• Charland N, Nizet V, Rubens CE, Kim KS, Lacouture S, Gottschalk M. Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells. Infect. Immun. 68 (2 ), 637 – 643 (2000).
   PubMed Web of Science ®Google Scholar
• Tenenbaum T, Adam R, Eggelnpohler I et al. Strain-dependent disruption of blood-cerebrospinal fluid barrier by Streptoccocus suis in vitro. FEMS Immunol. Med. Microbiol. 44 (1 ), 25 – 34 (2005).
   PubMedGoogle Scholar
• 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 8, 607 (2015).
   PubMedGoogle Scholar
• Chabot-Roy G, Willson P, Segura M, Lacouture S, Gottschalk M. Phagocytosis and killing of Streptococcus suis by porcine neutrophils. Microb. Pathog. 41 (1 ), 21 – 32 (2006).
   PubMed Web of Science ®Google Scholar
• 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. 132 (1 ), 211 – 219 (2008).
   PubMed Web of Science ®Google Scholar
• Segura M, Gottschalk M. Streptococcus suis interactions with the murine macrophage cell line J774: adhesion and cytotoxicity. Infect. Immun. 70 (8 ), 4312 – 4322 (2002).
   PubMed Web of Science ®Google Scholar
• Tanabe S, Gottschalk M, Grenier D. Hemoglobin and Streptococcus suis cell wall act in synergy to potentiate the inflammatory response of monocyte-derived macrophages. Innate Immun. 14 (6 ), 357 – 363 (2008).
   PubMed Web of Science ®Google Scholar
• Al-Numani D, Segura M, Dore M, Gottschalk M. Up-regulation of ICAM-1, CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes stimulated by Streptococcus suis serotype 2. Clin. Exp. Immunol. 133 (1 ), 67 – 77 (2003).
   PubMed Web of Science ®Google Scholar
• Seitz M, Beineke A, Seele J, Fulde M, Valentin-Weigand P, Baums CG. A novel intranasal mouse model for mucosal colonization by Streptococcus suis serotype 2. J. Med. Microbiol. 61 (Pt 9 ), 1311 – 1318 (2012).
   PubMed Web of Science ®Google Scholar
• Takeuchi D, Akeda Y, Nakayama T et al. The contribution of suilysin to the pathogenesis of Streptococcus suis meningitis. J. Infect. Dis. 209 (10 ), 1509 – 1519 (2014).
   PubMed Web of Science ®Google Scholar
• Charland N, Harel J, Kobisch M, Lacasse S, Gottschalk M. Streptococcus suis serotype 2 mutants deficient in capsular expression. Microbiology 144 (Pt 2 ), 325 – 332 (1998).
   PubMed Web of Science ®Google Scholar
• Tenenbaum T, Essmann F, Adam R et al. Cell death, caspase activation, and HMGB1 release of porcine choroid plexus epithelial cells during Streptococcus suis infection in vitro. Brain Res. 1100, 1 – 12 (2006).
   PubMed Web of Science ®Google Scholar
• 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. 6 (9 ), 867 – 881 (2004).
   PubMed Web of Science ®Google Scholar
• Meng F, Wu NH, Nerlich A, Herrler G, Valentin-Weigand P, Seitz M. Dynamic virus-bacterium interactions in a porcine precision-cut lung slice coinfection model: swine influenza virus paves the way for Streptococcus suis infection in a two-step process. Infect. Immun. 83 (7 ), 2806 – 2815 (2015).
   PubMed Web of Science ®Google Scholar
• Wang Y, Gagnon CA, Savard C 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. 81 (12 ), 4498 – 4508 (2013).
   PubMed Web of Science ®Google Scholar
• Lv Q, Hao H, Bi L, Zheng Y, Zhou X, Jiang Y. Suilysin remodels the cytoskeletons of humanbrain microvascular endothelial cells by activating RhoA and Rac1 GTPase. Protein Cell 5 (4 ), 261 – 264 (2014).
   PubMed Web of Science ®Google Scholar
• Kim KS. Mechanisms of microbial traversal of the blood–brain barrier.. Nat. Rev. Microbiol. 6 (8 ), 625 – 634 (2008).
   PubMed Web of Science ®Google Scholar
• 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. 204 (6 ), 919 – 929 (2011).
   PubMed Web of Science ®Google Scholar
• Vanier G, Segura M, Lecours MP, Grenier D, Gottschalk M. Porcine brain microvascular endothelial cell-derived interleukin-8 is first induced and then degraded by Streptococcus suis. Microb. Pathog. 46 (3 ), 135 – 143 (2009).
   PubMed Web of Science ®Google Scholar
• Segura M, Vanier G, Al-Numani D, Lacouture S, Olivier M, Gottschalk M. Proinflammatory cytokine and chemokine modulation by Streptococcus suis in a whole-blood culture system. FEMS Immunol. Med. Microbiol. 47 (1 ), 92 – 106 (2006).
   PubMedGoogle Scholar
• Zheng H, Punaro MC, Segura M et al. Toll-like receptor 2 is partially involved in the activation of murine astrocytes by Streptococcus suis an important zoonotic agent of meningitis. J. Neuroimmunol. 234 (1 ), 71 – 83 (2011).
   PubMed Web of Science ®Google Scholar
• Dominguez-Punaro Mde L, Segura M, Contreras I et al. In vitro characterization of the microglial inflammatory response to Streptococcus suis an important emerging zoonotic agent of meningitis. Infect. Immun. 78 (12 ), 5074 – 5085 (2010).
   PubMed Web of Science ®Google Scholar
• Du HM, Huang W, Xie HF et al. The genetically modified suilysin, rSLY(P353L), provides a candidate vaccine that suppresses proinflammatory response and reduces fatality following infection with Streptococcus suis. Vaccine 31 (38 ), 4209 – 4215 (2013).
   PubMed Web of Science ®Google Scholar
• Bi Y, Li J, Yang L et al. Assessment of the pathogenesis of Streptococcus suis type 2 infection in piglets for understanding streptococcal toxic shock-like syndrome, meningitis, and sequelae. Vet. Microbiol. 173 (3 ), 299 – 309 (2014).
   PubMed Web of Science ®Google Scholar
• Ye C, Zhu X, Jing H et al. Streptococcus suis sequence type 7 outbreak, Sichuan, China. Emerg. Infect. Dis. 12 (8 ), 1203 – 1208 (2006).
   PubMed Web of Science ®Google Scholar
• Takeuchi D, Kerdsin A, Pienpringam A et al. Population-based study of Streptococcus suis infection in humans in Phayao province in Northern Thailand. PLoS ONE 7 (2 ), e31265 (2012).
   PubMed Web of Science ®Google Scholar
• Kerdsin A, Dejsirilert S, Puangpatra P et al. Genotypic profile of Streptococcus suis serotype 2 and clinical features of infection in humans, Thailand. Emerg. Infect. Dis. 17 (5 ), 835 – 842 (2011).
   PubMed Web of Science ®Google Scholar
• Jacobs AaC, Vandenberg AJG, Loeffen PLW. Protection of experimentally infected pigs by suilysin, the thiol-activated haemolysin of Streptococcus suis. Vet. Rec. 139 (10 ), 225 – 228 (1996).
   PubMed Web of Science ®Google Scholar
• Segura M. Streptococcus suis vaccines: candidate antigens and progress. Expert Rev. Vaccines 14 (12 ), 1587 – 1608 (2015).
   PubMed Web of Science ®Google Scholar
• Baums CG, Bruggemann C, Kock C, Beineke A, Waldmann KH, Valentin-Weigand P. Immunogenicity of an autogenous Streptococcus suis bacterin in preparturient sows and their piglets in relation to protection after weaning. Clin. Vaccine Immunol. 17 (10 ), 1589 – 1597 (2010).
   PubMedGoogle Scholar
• Kock C, Beineke A, Seitz M et al. Intranasal immunization with a live Streptococcus suis isogenic ofs mutant elicited suilysin-neutralization titers but failed to induce opsonizing antibodies and protection. Vet. Immunol. Immunopathol. 132 (2 ), 135 – 145 (2009).
   PubMed Web of Science ®Google Scholar
• Liu L, Cheng G, Wang C et al. Identification and experimental verification of protective antigens against Streptococcus suis serotype 2 based on genome sequence analysis. Curr. Microbiol. 58 (1 ), 11 – 17 (2009).
   PubMed Web of Science ®Google Scholar