Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor
Meningococcal disease caused by serogroup B Neisseria meningitidis remains an important health problem in many parts of the world, and there are currently no comprehensive vaccines. Poor immunogenicity, combined with immunological identity to human sialic acids, have hindered the development of a se...
| Váldodahkkit: | , , , |
|---|---|
| Materiálatiipa: | Journal article |
| Giella: | English |
| Almmustuhtton: |
Microbiology Society
2010
|
| _version_ | 1826296749231177728 |
|---|---|
| author | Evans, N Harrison, O Clow, K al., E |
| author_facet | Evans, N Harrison, O Clow, K al., E |
| author_sort | Evans, N |
| collection | OXFORD |
| description | Meningococcal disease caused by serogroup B Neisseria meningitidis remains an important health problem in many parts of the world, and there are currently no comprehensive vaccines. Poor immunogenicity, combined with immunological identity to human sialic acids, have hindered the development of a serogroup B conjugate vaccine, resulting in the development of alternative vaccine candidates, including many outer-membrane protein (OMP)-based formulations. However, the design of protein-based meningococcal vaccines is complicated by the high level of genetic and antigenic diversity of the meningococcus. Knowledge of the extent and structuring of this diversity can have implications for the use of particular proteins as potential vaccine candidates. With this in mind, the diversity of the meningococcal OMP HmbR was investigated among N. meningitidis isolates representative of major hyper-invasive lineages. In common with other meningococcal antigens, the genetic diversity of hmbR resulted from a combination of intraspecies horizontal genetic exchange and de novo mutation. Furthermore, genealogical analysis showed an association of hmbR genes with clonal complexes and the occurrence of two hmbR families, A and B. Three variable regions (VR1–VR3), located in loops 2, 3 and 4, were observed with clonal complex structuring of VR types. A minority of codons (3.9 %), located within putative surface-exposed loop regions of a 2D model, were under diversifying selection, indicating regions of the protein likely to be subject to immune attack. |
| first_indexed | 2024-03-07T04:21:08Z |
| format | Journal article |
| id | oxford-uuid:cb0f4b38-f8da-4b00-8454-4e12bb44c876 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:21:08Z |
| publishDate | 2010 |
| publisher | Microbiology Society |
| record_format | dspace |
| spelling | oxford-uuid:cb0f4b38-f8da-4b00-8454-4e12bb44c8762022-03-27T07:12:03ZVariation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptorJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cb0f4b38-f8da-4b00-8454-4e12bb44c876EnglishSymplectic Elements at OxfordMicrobiology Society2010Evans, NHarrison, OClow, Kal., EMeningococcal disease caused by serogroup B Neisseria meningitidis remains an important health problem in many parts of the world, and there are currently no comprehensive vaccines. Poor immunogenicity, combined with immunological identity to human sialic acids, have hindered the development of a serogroup B conjugate vaccine, resulting in the development of alternative vaccine candidates, including many outer-membrane protein (OMP)-based formulations. However, the design of protein-based meningococcal vaccines is complicated by the high level of genetic and antigenic diversity of the meningococcus. Knowledge of the extent and structuring of this diversity can have implications for the use of particular proteins as potential vaccine candidates. With this in mind, the diversity of the meningococcal OMP HmbR was investigated among N. meningitidis isolates representative of major hyper-invasive lineages. In common with other meningococcal antigens, the genetic diversity of hmbR resulted from a combination of intraspecies horizontal genetic exchange and de novo mutation. Furthermore, genealogical analysis showed an association of hmbR genes with clonal complexes and the occurrence of two hmbR families, A and B. Three variable regions (VR1–VR3), located in loops 2, 3 and 4, were observed with clonal complex structuring of VR types. A minority of codons (3.9 %), located within putative surface-exposed loop regions of a 2D model, were under diversifying selection, indicating regions of the protein likely to be subject to immune attack. |
| spellingShingle | Evans, N Harrison, O Clow, K al., E Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor |
| title | Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor |
| title_full | Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor |
| title_fullStr | Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor |
| title_full_unstemmed | Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor |
| title_short | Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor |
| title_sort | variation and molecular evolution of hmbr the neisseria meningitidis haemoglobin receptor |
| work_keys_str_mv | AT evansn variationandmolecularevolutionofhmbrtheneisseriameningitidishaemoglobinreceptor AT harrisono variationandmolecularevolutionofhmbrtheneisseriameningitidishaemoglobinreceptor AT clowk variationandmolecularevolutionofhmbrtheneisseriameningitidishaemoglobinreceptor AT ale variationandmolecularevolutionofhmbrtheneisseriameningitidishaemoglobinreceptor |