title: Molecular mechanism by which surface antigen HP0197 mediates host cell attachment in the pathogenic bacteria Streptococcus suis.
abstract: Streptococcus suis, one of the most important and prevalent pathogens in swine, presents a major challenge to global public health. HP0197 is an S. suis surface antigen that was previously identified by immunoproteomics and can bind to the host cell surface. Here, we investigated the interaction between HP0197 and the host cell surface glycosaminoglycans (GAGs) using indirect immunofluorescence and cell adhesion inhibition assays. In addition, we determined that a novel 18-kDa domain in the N-terminal region of HP0197 functions as the GAG-binding domain. We then solved the three-dimensional structures of the N-terminal 18-kDa and C-terminal G5 domains using x-ray crystallography. Based on this structural information, the GAG-binding sites in HP0197 were predicted and subsequently verified using site-directed mutagenesis and indirect immunofluorescence. The results indicate that the positively charged residues on the exposed surface of the 18-kDa domain, which are primarily lysines, likely play a critical role in the HP0197-heparin interaction that mediates bacterium-host cell adhesion. Understanding this molecular mechanism may provide a basis for the development of effective drugs and therapeutic strategies for treating streptococcal infections.
authors.affiliation: Unit of Animal Infectious Diseases, National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Zeng-zhi
authors.initials: ZZ
authors.lastname: Yuan
authors.forename: Xiao-jie
authors.initials: XJ
authors.lastname: Yan
authors.forename: An-ding
authors.initials: AD
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Yue-quan
authors.initials: YQ
authors.lastname: Shen
authors.forename: Mei-lin
authors.initials: ML
authors.lastname: Jin
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D001422:Bacterial Adhesion; D001666:Binding Sites, Antibody; D002460:Cell Line; D006801:Humans; D008958:Models, Molecular; D055672:Static Electricity; D017011:Streptococcus suis / Q000276:immunology / Q000502:physiology*
chemical_list: D000907:Antibodies, Bacterial; D000954:Antigens, Surface