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The major fimbrial subunit of Bordetella pertussis binds to sulfated sugars
C A Geuijen1, R J Willems, F R Mooi
1Molecular Microbiology Unit, National Institute of Health and Environmental Protection, The Netherlands.
Abstract:
Bordetella pertussis fimbriae are composed of major and minor subunits, and recently it was shown that the minor fimbrial subunit binds to Vla-5, a receptor located on monocytes (W. Hazenbos, C. Geuijen, B. van den Berg, F. Mooi, and R. van Furth, J. Infect. Dis. 171:924-929, 1995). Here we present evidence that the major subunits bind to sulfated sugars, which are ubiquitous in the respiratory tract. Binding was observed to chondroitin sulfate, heparan sulfate, and dextran sulfate but not to dextran. Removal of the minor subunit from fimbriae did not significantly affect binding to sulfated sugars, indicating that the major subunit alone is sufficient for this binding. Fimbriae were also able to bind HEp-2 cells, which are known to display glycoconjugates on their surface. This binding was not dependent on the presence of the minor subunit. However, binding was dependent on the sulfation state of the glycoconjugates, since inhibition of the sulfation resulted in a significant reduction of fimbria binding. The specificity of fimbria binding was further characterized by using heparan sulfate-derived disaccharides in inhibition assays. Two disaccharides were highly effective inhibitors, and it was observed that both the degree of sulfation and the arrangement of the sulfate groups on the disaccharides were important for binding to fimbriae. B. pertussis bacteria also bound to sulfated sugars and HEp-2 cells, and analysis of B. pertussis mutants indicated that both filamentous hemagglutinin and fimbriae were required for this binding. A host protein present in the extracellular matrix, fibronectin, has binding activities similar to those of B. pertussis fimbriae, binding to both Vla-5 and sulfated sugars. Two regions in the major fimbrial subunit were identified which showed similarity with fibronectin peptides which bind to sulfated sugars. Thus, B. pertussis fimbriae exemplify molecular mimicry and may co-opt host processes by mimicking natural ligand-receptor interactions.
Insights
Bordetella pertussis fimbriae’s major subunits bind to sulfated sugars in the respiratory tract, mimicking host interactions. This binding is crucial for bacterial adhesion and may involve molecular mimicry.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- Bordetella pertussis fimbriae have major and minor subunits.
- The minor subunit binds to the Vla-5 receptor on monocytes.
- Sulfated sugars are common in the respiratory tract.
Purpose of the Study:
- To investigate the binding properties of B. pertussis fimbriae major subunits.
- To determine the role of sulfated sugars in fimbrial adhesion.
- To explore potential molecular mimicry by B. pertussis fimbriae.
Main Methods:
- Binding assays using purified fimbriae and sulfated sugars (chondroitin sulfate, heparan sulfate, dextran sulfate).
- HEp-2 cell binding assays with varying sulfation states.
- Analysis of B. pertussis mutants lacking filamentous hemagglutinin and fimbriae.
- Comparison of fimbrial binding with host protein fibronectin.
Main Results:
- B. pertussis fimbriae major subunits bind to sulfated sugars, independent of the minor subunit.
- Fimbriae bind to HEp-2 cells, dependent on the sulfation of cell surface glycoconjugates.
- Bacterial binding requires both filamentous hemagglutinin and fimbriae.
- Fimbriae share binding similarities with fibronectin, suggesting molecular mimicry.
Conclusions:
- The major subunit of B. pertussis fimbriae mediates binding to respiratory tract sulfated sugars.
- This binding mechanism may facilitate bacterial adhesion and colonization.
- B. pertussis fimbriae exhibit molecular mimicry, potentially exploiting host ligand-receptor interactions.