Role of the conserved C-repeat region of the M protein of Streptococcus pyogenes.
The surface-located M protein functions to protect Streptococcus pyogenes (the group A streptococcus) from phagocytosis by polymorphonuclear leukocytes. It has been suggested that this protection results from the ability of M protein to bind factor H, a serum protein that can inhibit the activation of complement. Among different serological variants of M protein, the C-repeat domain is highly conserved and is exposed on the bacterial surface. This domain has been implicated in binding to complement factor H and in M-protein-mediated adherence of streptococci to human keratinocytes in the cutaneous epithelium. In this study, we constructed an S. pyogenes mutant strain which expresses an M6 protein from which the entire C-repeat domain was deleted. As predicted, this mutant did not adhere well to human keratinocytes and was unable to bind to factor H. Unexpectedly, the mutant was able to survive and multiply in human blood. Therefore, while the binding of factor H and the facilitation of adherence to keratinocytes appear to involve recognition of the C-repeat domain, a region of the M-protein molecule distinct from the C-repeat domain confers upon S. pyogenes its ability to resist phagocytosis.
Perez-Casal
J
J
Department of Microbiology and Immunology, Emory University Health Sciences Center, Atlanta, Georgia 30322, USA.
Okada
N
N
Caparon
M G
MG
Scott
J R
JR
D000483:Alleles; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D002352:Carrier Proteins; D003001:Cloning, Molecular; D017242:Complement Factor H / Q000378:metabolism; D017124:Conserved Sequence; D017353:Gene Deletion; D015603:Keratinocytes / Q000382:microbiology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010587:Phagocytosis; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D013297:Streptococcus pyogenes / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C493495:CFH protein, human; D002352:Carrier Proteins; C014689:streptococcal M protein; D017242:Complement Factor H