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Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria
H Källström1, M K Liszewski, J P Atkinson
1Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Abstract:
Pili of Neisseria gonorrhoeae and Neisseria meningitidis mediate binding of the bacteria to human cell-surface receptors. We found that purified pili bound to a 55- to 60-kDa doublet band on SDS-PAGE of separated human epithelial cell extracts. This is a migration pattern typical of membrane cofactor protein (MCP or CD46). MCP is a widely distributed human complement regulatory protein. Attachment of the bacteria to epithelial cells was blocked by polyclonal and monoclonal antibodies directed against MCP, suggesting that this complement regulator is a receptor for piliated Neisseria. We proved this hypothesis by demonstrating that piliated, but not non-piliated, gonococci bound to CHO cells transfected with human MCP-cDNA. We also demonstrated a direct interaction between purified recombinant MCP and piliated Neisseria. Finally, recombinant MCP protein produced in E. coli inhibited attachment of the bacteria to target cells. Taken together, our data show that MCP is a human cell-surface receptor for piliated pathogenic Neisseria.
Insights
Pathogenic Neisseria bacteria use pili to bind human cells. Researchers identified Membrane Cofactor Protein (MCP/CD46) as the specific cell-surface receptor for these bacteria, confirming its role in Neisseria attachment.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Pili are crucial for Neisseria gonorrhoeae and Neisseria meningitidis adherence to host cells.
- Identifying bacterial adhesin receptors is key to understanding pathogenesis.
Purpose of the Study:
- To identify the human cell-surface receptor for piliated pathogenic Neisseria.
- To elucidate the role of Membrane Cofactor Protein (MCP/CD46) in bacterial attachment.
Main Methods:
- SDS-PAGE analysis of human epithelial cell extracts to identify potential binding proteins.
- Antibody blocking assays using anti-MCP antibodies.
- Bacterial binding assays with MCP-transfected cells and recombinant MCP.
Main Results:
- Purified pili bound to a 55- to 60-kDa protein band, characteristic of Membrane Cofactor Protein (MCP/CD46).
- Anti-MCP antibodies blocked bacterial attachment.
- Piliated Neisseria bound to cells expressing human MCP and directly interacted with recombinant MCP.
Conclusions:
- Membrane Cofactor Protein (MCP/CD46) serves as a human cell-surface receptor for piliated pathogenic Neisseria.
- This interaction is critical for the initial attachment of these bacteria to host epithelial cells.