title: Group A streptococcus adheres to pharyngeal epithelial cells with salivary proline-rich proteins via GrpE chaperone protein.
abstract: Group A Streptococcus pyogenes (GAS) is an important human pathogen that frequently causes pharyngitis. GAS organisms can adhere to and invade pharyngeal epithelial cells, which are overlaid by salivary components. However, the role of salivary components in GAS adhesion to pharyngeal cells has not been reported precisely. We collected human saliva and purified various salivary components, including proline-rich protein (PRP), statherin, and amylase, and performed invasion assays. The GAS-HEp-2 association ratio (invasion/adhesion ratio) and invasion ratio of GAS were increased significantly with whole human saliva and PRP, while the anti-PRP antibody inhibited the latter. GAS strain NY-5, which lacks M and F proteins on the cell surface, was promoted to cohere with HEp-2 cells by whole human saliva and PRP. The 28-kDa protein of GAS bound to PRP and was identified as GrpE, a chaperone protein, whereas the N-terminal of GrpE was found to bind to PRP. A GrpE-deficient mutant of GAS strain B514Sm, TR-45, exhibited a reduced ability to adhere to and invade HEp-2 cells. Microscopic observations showed the GrpE was mainly expressed on the surface of the cell division site of GAS. Furthermore, GrpE-deficient mutants of GAS and Streptococcus pneumoniae showed an elongated morphology as compared with the wild type. Taken together, this is the first study to show an interaction between salivary PRP and GAS GrpE, which plays an important role in GAS infection on the pharynx, whereas the expression of GrpE on the surface of GAS helps to maintain morphology.
authors.affiliation: Division of Special Care Dentistry, Osaka University Graduate School of Dentistry, Suita, Osaka, 565-0871, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Murakami
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Terao
authors.forename: Ichijiro
authors.initials: I
authors.lastname: Morisaki
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Hamada
authors.forename: Shigetada
authors.initials: S
authors.lastname: Kawabata
mesh_terms: D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins / Q000378:metabolism; D012463:Saliva / Q000382:microbiology; D055273:Salivary Proline-Rich Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; C068113:GrpE protein, Bacteria; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; D055273:Salivary Proline-Rich Proteins