title: The genetically modified suilysin, rSLY(P353L), provides a candidate vaccine that suppresses proinflammatory response and reduces fatality following infection with Streptococcus suis.
abstract: Streptococcus suis is a persistent global hazard in the swine industry and an emerging threat to public health. The high mortality in China following outbreaks of streptococcal toxic shock syndrome (STSS) underscores the urgency for effective prevention. A limited understanding of the pathogenesis of S. suis in STSS may explain the lack of biological products for prevention. Suilysin (SLY) is an important virulence factor in the pathogenesis of S. suis. To identify a candidate vaccine for S. suis-induced STSS, we constructed a recombinant non-hemolytic mutant of SLY that has hemagglutination activity, rSLY(P353L), and evaluated its ability to induce inflammatory response and prevent fatal S. suis infection in mice. The rSLY(P353L) mutant, as compared with hemolytic rSLY, elicited lower levels of IL-6, KC and IL-10 at 3h and 5h post-treatment (p<0.05), indicating that hemolytic activity is associated with rSLY-mediated inflammation. Furthermore, passive immunization with anti-SLY(P353L) antisera protected mice from acute death after infection with S. suis SC84 (p<0.05). Effects were not due to protection against tissue damage, as S. suis SC84 caused no detectable histopathological lesions in mice within 24h. However, immunization with rSLY(P353L) caused significantly reduced levels of KC and IL-1β at 6 and 9h post-challenge and IL-6 at 9h post-challenge (p<0.05). In conclusion, rSLY(P353L) may provide a potential vaccine for protection against S. suis-induced STSS due to its reduction in proinflammatory response early in S. suis infection.
authors.affiliation: College of Biotechnology, Southwest University, Beibei, Chongqing, China.
authors.forename: Huamao
authors.initials: H
authors.lastname: Du
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Hefang
authors.initials: H
authors.lastname: Xie
authors.forename: Changyun
authors.initials: C
authors.lastname: Ye
authors.forename: Huaiqi
authors.initials: H
authors.lastname: Jing
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Ren
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D005260:Female; D006460:Hemolysin Proteins / Q000235:genetics* / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013290:Streptococcal Infections / Q000401:mortality / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D017011:Streptococcus suis / Q000472:pathogenicity*; D013552:Swine
chemical_list: D006460:Hemolysin Proteins; D015850:Interleukin-6; D022541:Streptococcal Vaccines; C104760:suilysin; D016753:Interleukin-10
keywords: CDC; CFU; HUs; IL-1β; IL-6; Inflammatory cytokine; Mutagenesis; PBS; STSS; Streptococcal toxic shock syndrome; Streptococcus suis; Suilysin; TNF-α; cholesterol-dependent cytolysin; colony forming units; hemoagglutination units; i.p.; interleukin 1β; interleukin 6; intraperitonally; phosphate buffered saline; rSLY; recombinant suilysin; streptococcal toxic shock syndrome; tumor necrosis factor alpha