title: Membrane cofactor protein (MCP, CD46) binding to clinical isolates of Streptococcus pyogenes: binding to M type 18 strains is independent of Emm or Enn proteins.
abstract: The complement regulatory protein CD46 (MCP, membrane cofactor protein) is used as a cell receptor by a number of bacterial and viral pathogens, including Streptococcus pyogenes (Group A Streptococci). The highly variable M (Emm) proteins are virulence factors of S. pyogenes, and Emm proteins of serotypes 5, 6 or 22 are able of binding to CD46, thus mediating the binding of Streptococci to human cells. In this work, using a soluble construction encompassing the extracellular domain of human CD46, we have analyzed its binding to clinical isolates of S. pyogenes, including isolates of the M types 1, 3 and 18 that are frequently found in invasive infections or rheumatic fever. Our data show a strong binding of CD46 to bacteria of M types 1, 3, 8, 18, 24, 28, 29, 31 and 78; weak binding to M6 and M29 and no binding to M types 11, 12, M27 or M30. Surprisingly, CD46 bound to isogenic mutants of one clinical M18 isolate lacking the Emm protein or Emm and the Emm-related protein Enn, regardless of having capsule or not. In addition, these isogenic mutants bound to keratinocytes in a CD46-dependent manner, confirming the role of CD46 as one of the cell receptors for Group A Streptococci. Furthermore, CD46 did not bind to a recombinant Emm 18 construct, confirming that Emm is not involved in CD46 binding to M18 bacteria. Emm-dependent and -independent CD46 binding of clinical isolates of Streptococci confirms the importance of CD46 as a cell target that might confer pathogens some biological advantages over the host.
authors.affiliation: Department of Cellular and Molecular Pathophysiology, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain. mjfeito@bbm1.ucm.es <mjfeito@bbm1.ucm.es>
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Feito
authors.forename: Alejandra
authors.initials: A
authors.lastname: Sánchez
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Oliver
authors.forename: David
authors.initials: D
authors.lastname: Pérez-Caballero
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodríguez de Córdoba
authors.forename: Sebastián
authors.initials: S
authors.lastname: Albertí
authors.forename: Jose M
authors.initials: JM
authors.lastname: Rojo
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000382:microbiology; D051916:Membrane Cofactor Protein / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010587:Phagocytosis; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000145:classification* / Q000302:isolation & purification*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; C088686:Enn protein, Streptococcus pyogenes; D051916:Membrane Cofactor Protein; D011994:Recombinant Proteins; C014689:streptococcal M protein