Abstract
The pathogenic Gram-positive bacterium Streptococcus pyogenes (group A streptococcus) is the causative agent of numerous suppurative diseases of human skin. The M protein of S. pyogenes mediates the adherence of the bacterium to keratinocytes, the most numerous cell type in the epidermis. In this study, we have constructed and analyzed a series of mutant M proteins and have shown that the C repeat domain of the M molecule is responsible for cell recognition. The binding of factor H, a serum regulator of complement activation, to the C repeat region of M protein blocked bacterial adherence. Factor H is a member of a large family of complement regulatory proteins that share a homologous structural motif termed the short consensus repeat. Membrane cofactor protein (MCP), or CD46, is a short consensus repeat-containing protein found on the surface of keratinocytes, and purified MCP could competitively inhibit the adherence of S. pyogenes to these cells. Furthermore, the M protein was found to bind directly to MCP, whereas mutant M proteins that lacked the C repeat domain did not bind MCP, suggesting that recognition of MCP plays an important role in the ability of the streptococcus to adhere to keratinocytes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Bacterial / metabolism
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Antigens, CD / biosynthesis
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Antigens, CD / chemistry
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Antigens, CD / metabolism*
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Bacterial Adhesion*
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Bacterial Outer Membrane Proteins*
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Bacterial Proteins / biosynthesis
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Bacterial Proteins / chemistry
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Bacterial Proteins / metabolism*
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Base Sequence
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Binding, Competitive
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Carrier Proteins*
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Cloning, Molecular
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Consensus Sequence
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DNA Primers
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Humans
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Keratinocytes / microbiology*
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Keratinocytes / physiology
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Membrane Cofactor Protein
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / metabolism*
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Models, Structural
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Molecular Sequence Data
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Polymerase Chain Reaction
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / metabolism
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Repetitive Sequences, Nucleic Acid
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Restriction Mapping
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Streptococcus pyogenes / physiology*
Substances
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Antigens, Bacterial
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Antigens, CD
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Bacterial Outer Membrane Proteins
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Bacterial Proteins
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CD46 protein, human
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Carrier Proteins
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DNA Primers
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Membrane Cofactor Protein
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Membrane Glycoproteins
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Recombinant Fusion Proteins
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Recombinant Proteins
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streptococcal M protein