title: The non-conserved region of MRP is involved in the virulence of Streptococcus suis serotype 2.
abstract: Muramidase-released protein (MRP) of Streptococcus suis serotype 2 (SS2) is an important epidemic virulence marker with an unclear role in bacterial infection. To investigate the biologic functions of MRP, 3 mutants named Δmrp, Δmrp domain 1 (Δmrp-d1), and Δmrp domain 2 (Δmrp-d2) were constructed to assess the phenotypic changes between the parental strain and the mutant strains. The results indicated that MRP domain 1 (MRP-D1, the non-conserved region of MRP from a virulent strain, a.a. 242-596) played a critical role in adherence of SS2 to host cells, compared with MRP domain 1* (MRP-D1*, the non-conserved region of MRP from a low virulent strain, a.a. 239-598) or MRP domain 2 (MRP-D2, the conserved region of MRP, a.a. 848-1222). We found that MRP-D1 but not MRP-D2, could bind specifically to fibronectin (FN), factor H (FH), fibrinogen (FG), and immunoglobulin G (IgG). Additionally, we confirmed that mrp-d1 mutation significantly inhibited bacteremia and brain invasion in a mouse infection model. The mrp-d1 mutation also attenuated the intracellular survival of SS2 in RAW246.7 macrophages, shortened the growth ability in pig blood and decreased the virulence of SS2 in BALB/c mice. Furthermore, antiserum against MRP-D1 was found to dramatically impede SS2 survival in pig blood. Finally, immunization with recombinant MRP-D1 efficiently enhanced murine viability after SS2 challenge, indicating its potential use in vaccination strategies. Collectively, these results indicated that MRP-D1 is involved in SS2 virulence and eloquently demonstrate the function of MRP in pathogenesis of infection.
authors.affiliation: a Key Lab of Animal Bacteriology, OIE Reference Lab for Swine Streptococcosis, College of Veterinary Medicine, Ministry of Agriculture , Nanjing Agricultural University , Nanjing , China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.affiliation: a Key Lab of Animal Bacteriology, OIE Reference Lab for Swine Streptococcosis, College of Veterinary Medicine, Ministry of Agriculture , Nanjing Agricultural University , Nanjing , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fu
authors.affiliation: a Key Lab of Animal Bacteriology, OIE Reference Lab for Swine Streptococcosis, College of Veterinary Medicine, Ministry of Agriculture , Nanjing Agricultural University , Nanjing , China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Ma
authors.affiliation: a Key Lab of Animal Bacteriology, OIE Reference Lab for Swine Streptococcosis, College of Veterinary Medicine, Ministry of Agriculture , Nanjing Agricultural University , Nanjing , China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: He
authors.affiliation: a Key Lab of Animal Bacteriology, OIE Reference Lab for Swine Streptococcosis, College of Veterinary Medicine, Ministry of Agriculture , Nanjing Agricultural University , Nanjing , China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Yu
authors.affiliation: a Key Lab of Animal Bacteriology, OIE Reference Lab for Swine Streptococcosis, College of Veterinary Medicine, Ministry of Agriculture , Nanjing Agricultural University , Nanjing , China.
authors.forename: Dechao
authors.initials: D
authors.lastname: Du
authors.affiliation: a Key Lab of Animal Bacteriology, OIE Reference Lab for Swine Streptococcosis, College of Veterinary Medicine, Ministry of Agriculture , Nanjing Agricultural University , Nanjing , China.
authors.forename: Huochun
authors.initials: H
authors.lastname: Yao
authors.affiliation: a Key Lab of Animal Bacteriology, OIE Reference Lab for Swine Streptococcosis, College of Veterinary Medicine, Ministry of Agriculture , Nanjing Agricultural University , Nanjing , China.
authors.forename: Chengping
authors.initials: C
authors.lastname: Lu
authors.affiliation: a Key Lab of Animal Bacteriology, OIE Reference Lab for Swine Streptococcosis, College of Veterinary Medicine, Ministry of Agriculture , Nanjing Agricultural University , Nanjing , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D000072417:Protein Domains; D000067996:RAW 264.7 Cells; D016415:Sequence Alignment; D065288:Serogroup; D013290:Streptococcal Infections / Q000382:microbiology / Q000662:veterinary*; D017011:Streptococcus suis / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D013552:Swine; D013553:Swine Diseases / Q000382:microbiology*; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; C421489:MRP protein, Streptococcus suis; D017242:Complement Factor H; D005340:Fibrinogen
keywords: Streptococcus suis serotype 2; infection; muramidase-released protein; vaccine; virulence