title: Hyaluronic acid capsule modulates M protein-mediated adherence and acts as a ligand for attachment of group A Streptococcus to CD44 on human keratinocytes.
abstract: We used wild-type and isogenic mutant strains of group A Streptococcus (GAS) that expressed M protein, capsule, or both to study the function of M protein and the hyaluronic acid capsular polysaccharide in attachment of GAS to human keratinocytes. Types 6 and 24, but not type 18, M protein were found to mediate attachment of GAS to soft palate or skin keratinocytes, but this interaction was prevented by the hyaluronic acid capsule on highly encapsulated, or mucoid, strains. Monoclonal antibody to CD44, the principal hyaluronic acid-binding receptor on keratinocytes, inhibited attachment of both highly encapsulated and poorly encapsulated wild type strains of GAS, but not the attachment of acapsular mutants. Transfection of K562 cells with cDNA encoding human CD44 conferred the capacity to bind each of six wild-type strains of GAS, but not to bind acapsular mutants. Because, in contrast to other potential adhesins, the group A streptococcal capsule is both highly conserved and surface-exposed, it may serve as a universal adhesin for attachment of diverse strains of GAS to keratinocytes of the pharyngeal mucosa and the skin.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Schrager
authors.forename: S
authors.initials: S
authors.lastname: Albertí
authors.forename: C
authors.initials: C
authors.lastname: Cywes
authors.forename: G J
authors.initials: GJ
authors.lastname: Dougherty
authors.forename: M R
authors.initials: MR
authors.lastname: Wessels
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D000942:Antigens, Bacterial; D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008024:Ligands; D008856:Microscopy, Fluorescence; D009154:Mutation; D016133:Polymerase Chain Reaction; D013290:Streptococcal Infections / Q000209:etiology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014162:Transfection
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D018960:Hyaluronan Receptors; D008024:Ligands; C014689:streptococcal M protein; D006820:Hyaluronic Acid