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 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.
National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.|Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Nicholas J
NJ
Evans
The Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
Odile B
OB
Harrison
National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Kirsten
K
Clow
Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Jeremy P
JP
Derrick
National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Ian M
IM
Feavers
The Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
Martin C J
MCJ
Maiden
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D011995:Recombination, Genetic; D012641:Selection, Genetic
D001426:Bacterial Proteins; C094109:HmbR protein, Neisseria meningitidis; D011956:Receptors, Cell Surface