title: Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/factor H-like protein 1 to M18 strains involves two different cell surface molecules.
abstract: Streptococcus pyogenes, or group A Streptococcus, is one of the most frequent causes of pharyngitis and skin infections in humans. Many virulence mechanisms have been suggested to be involved in the infectious process. Among them is the binding to the bacterial cell surface of the complement regulatory proteins factor H, factor H-like protein 1 (FHL-1), and C4b-binding protein. Previous studies indicate that binding of these three regulators to the streptococcal cell involves the M protein encoded by the emm gene. M-type 18 strains are prevalent among clinical isolates and have been shown to interact with all three complement regulators simultaneously. Using isogenic strains lacking expression of the Emm18 or the Enn18 proteins, we demonstrate in this study that, in contradistinction to previously described S. pyogenes strains, M18 strains bind the complement regulators factor H, FHL-1, and C4b-binding protein through two distinct cell surface proteins. Factor H and FHL-1 bind to the Emm18 protein, while C4BP binds to the Enn18 protein. We propose that expression of two distinct surface structures that bind complement regulatory proteins represents a unique adaptation of M18 strains that enhances their resistance to opsonization by human plasma and increases survival of this particular S. pyogenes strain in the human host. These new findings illustrate that S. pyogenes has evolved diverse mechanisms for recruitment of complement regulatory proteins to the bacterial surface to evade immune clearance in the human host.
authors.affiliation: Departamento de Inmunología, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Pérez-Caballero
authors.forename: Isabel
authors.initials: I
authors.lastname: García-Laorden
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Cortés
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wessels
authors.forename: Santiago Rodríguez
authors.initials: SR
authors.lastname: de Córdoba
authors.forename: Sebastián
authors.initials: S
authors.lastname: Albertí
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000378:metabolism* / Q000502:physiology; D001422:Bacterial Adhesion / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism* / Q000502:physiology; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D017242:Complement Factor H / Q000378:metabolism*; D003169:Complement Inactivator Proteins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D012703:Serotyping; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000145:classification / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001798:Blood Proteins; C493495:CFH protein, human; D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; C099984:Enn18 protein, Streptococcus pyogenes; D006023:Glycoproteins; C100631:factor H-related protein 1; C014689:streptococcal M protein; D017242:Complement Factor H