Related Experiment Videos
Sequence variability of FrpB, a major iron-regulated outer-membrane protein in the pathogenic neisseriae
P van der Ley1, J van der Biezen, R Sutmuller
1Laboratory of Vaccine Development and Immune Mechanisms, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. peterl@rivm.nl
Abstract:
The FrpB protein from pathogenic neisseriae is a 77 kDa iron-regulated outer-membrane protein that belongs to the family of TonB-dependent receptors and may have potential as a vaccine component. Comparison between the frpB gene from three different meningococcal strains and a published gonococcal one revealed that the region from residues 350 to 390 displays pronounced sequence variability. In a model for the topology of FrpB in the outer membrane, this region corresponds to loop 7, the longest of the predicted 13 surface-exposed loops. Binding of four out of a total of eight bactericidal monoclonal antibodies to synthetic peptides corresponding to loop 7 showed that their epitopes are located here. The frpB genes from five additional meningococcal strains were cloned and sequenced in this region. Pairwise comparisons showed different degrees of similarity.
Insights
The FrpB protein
Area of Science:
- Microbiology and Immunology
- Bacterial Pathogenesis
- Vaccine Development
Background:
- FrpB is an iron-regulated outer-membrane protein in pathogenic Neisseria.
- It is a TonB-dependent receptor with potential as a vaccine candidate.
- Sequence variability in FrpB could impact vaccine efficacy.
Purpose of the Study:
- To investigate the sequence variability of the frpB gene in Neisseria meningitidis and Neisseria gonorrhoeae.
- To identify the location of epitopes for bactericidal monoclonal antibodies on the FrpB protein.
- To assess the potential of FrpB as a vaccine component.
Main Methods:
- Comparative sequencing of the frpB gene from multiple Neisseria strains.
- Bioinformatic analysis of FrpB protein topology and surface-exposed regions.
- Epitope mapping using synthetic peptides and monoclonal antibody binding assays.
Main Results:
- A highly variable region (residues 350-390) was identified in the frpB gene, corresponding to surface-exposed loop 7.
- Four bactericidal monoclonal antibodies recognized epitopes within this loop 7 region.
- Sequence analysis of additional meningococcal strains confirmed varying degrees of similarity in this region.
Conclusions:
- The variable loop 7 of FrpB is a key target for bactericidal antibodies.
- Sequence diversity in this region may influence the effectiveness of FrpB-based vaccines.
- Further research is needed to optimize FrpB as a broadly protective vaccine component against pathogenic Neisseria.