title: A Streptococcus suis LysM domain surface protein contributes to bacterial virulence.
abstract: Streptococcus suis (SS) is a major swine pathogen, as well as a zoonotic agent for humans. Numerous factors contribute to SS virulence, but the pathogenesis of SS infection is poorly understood. Here, we show that a novel SS surface protein containing a LysM at the N-terminus (SS9-LysM) contributes to SS virulence. Homology analysis revealed that the amino acid sequence of SS9-LysM from the SS strain GZ0565 shares 99.8-68.7% identity with homologous proteins from other SS strains and 41.2% identity with Group B Streptococcal protective antigen Sip. Immunization experiments showed that 7 out of 30 mice immunized with recombinant SS9-LysM were protected against challenge with the virulent GZ0565 strain, while all of the control mice died within 48h following bacterial challenge. In mouse infection model, the virulence of the SS9-LysM deletion mutant (ΔSS9-LysM) was reduced compared with the wild-type (WT) strain GZ0565 and SS9-LysM complemented strain. In addition, ΔSS9-LysM was significantly more sensitive to killing by pig blood ex vivo and mouse blood in vivo compared with the WT strain and SS9-LysM complemented strain. In vivo transcriptome analysis in mouse blood showed that the WT strain reduced the expression of host genes related to iron-binding by SS9-LysM. Moreover, the total free iron concentration in blood from infected mice was significantly lower for the ΔSS9-LysM strain compared with the WT strain. Together, our data reveal that SS9-LysM facilitates SS survival within blood by releasing more free iron from the host. This represents a new mechanism of SS pathogenesis.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China. Electronic address: wuzongfu@njau.edu.cn.
authors.forename: Zongfu
authors.initials: Z
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ren
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Tang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Zhou
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Dai
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Lai
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Huochun
authors.initials: H
authors.lastname: Yao
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Fan
authors.affiliation: Novel Bioinformatics Co., Ltd., Shanghai, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Chen
authors.affiliation: Novel Bioinformatics Co., Ltd., Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zong
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China. Electronic address: lucp@njau.edu.cn.
authors.forename: Chengping
authors.initials: C
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D001428:Bacterial Vaccines / Q000276:immunology; D001769:Blood / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000502:physiology*; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D050296:Microbial Viability / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D017011:Streptococcus suis / Q000235:genetics* / Q000472:pathogenicity*; D059467:Transcriptome; D014774:Virulence / Q000235:genetics*
chemical_list: D001428:Bacterial Vaccines; D008565:Membrane Proteins; D011994:Recombinant Proteins; D007501:Iron
keywords: Bacterial virulence; Iron; LysM domain; Streptococcus suis