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.
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.
Feito
Maria Jose
MJ
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>
Sánchez
Alejandra
A
Oliver
Maria Antonia
MA
Pérez-Caballero
David
D
Rodríguez de Córdoba
Santiago
S
Albertí
Sebastián
S
Rojo
Jose M
JM
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*
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