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Antibody response to fibronectin-binding adhesin FnbpA in patients with Staphylococcus aureus infections
1Department of Biochemistry, University of Pavia, 27100 Pavia, Italy.
Abstract:
We have analyzed antibody reactivity to a fibronectin-binding microbial surface component that recognizes adhesive matrix molecules (MSCRAMM) in blood plasma collected from patients with staphylococcal infections. All patients had elevated levels of anti-MSCRAMM antibodies compared to those of young children who, presumably, had not been exposed to staphylococcal infections. The anti-MSCRAMM antibodies preferentially reacted with the ligand-binding repeat domain of the adhesin. However, these antibodies did not inhibit fibronectin binding. Essentially, all patients had antibodies which specifically recognized the fibronectin-MSCRAMM complex but not the isolated components. Epitopes recognized by these anti-ligand-induced binding sites antibodies were found in each repeat unit of the MSCRAMM. These results demonstrate that staphylococci have bound fibronectin some time during infection and that each repeat unit in the MSCRAMM can engage in ligand binding. Furthermore, our previously proposed model, suggesting that an unordered structure in the MSCRAMM undergoes a conformational change upon ligand binding (K. House-Pompeo, Y. Xu, D. Joh, P. Speziale, and M. Höök, J. Biol. Chem. 271:1379-1384, 1996), is presumably operational in patients during infections.
Insights
Patients with staphylococcal infections show elevated antibodies against fibronectin-binding microbial surface components (MSCRAMM). These antibodies recognize the fibronectin-MSCRAMM complex, indicating bacterial fibronectin binding during infection.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Staphylococcal infections are a significant health concern.
- Microbial surface components recognizing adhesive matrix molecules (MSCRAMM) mediate bacterial adhesion to host tissues.
- Fibronectin is a key matrix molecule involved in bacterial adhesion.
Purpose of the Study:
- To analyze antibody reactivity to fibronectin-binding MSCRAMM in patients with staphylococcal infections.
- To investigate the nature of antibody recognition of the fibronectin-MSCRAMM complex.
- To validate a model of MSCRAMM conformational changes upon ligand binding.
Main Methods:
- Analysis of antibody reactivity in blood plasma from staphylococcal infection patients and young children.
- Characterization of antibody binding to isolated MSCRAMM and the fibronectin-MSCRAMM complex.
- Epitope mapping of anti-MSCRAMM antibodies.
Main Results:
- Patients with staphylococcal infections exhibited elevated anti-MSCRAMM antibody levels compared to controls.
- Antibodies preferentially recognized the ligand-binding repeat domain of MSCRAMM but did not inhibit fibronectin binding.
- Antibodies specifically recognized the fibronectin-MSCRAMM complex, with epitopes distributed across MSCRAMM repeat units.
- Evidence supports a conformational change model for MSCRAMM upon fibronectin binding.
Conclusions:
- Staphylococci bind fibronectin during infection, engaging each MSCRAMM repeat unit in ligand binding.
- The findings support a model where MSCRAMM undergoes conformational changes upon fibronectin binding in patients.
- Antibody responses in patients target the fibronectin-MSCRAMM complex, providing insights into host-pathogen interactions.