Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor
Open Access
- 1 May 2010
- journal article
- research article
- Published by Microbiology Society in Microbiology
- Vol. 156 (5), 1384-1393
- https://doi.org/10.1099/mic.0.036475-0
Abstract
Meningococcal disease caused by serogroup BNeisseria meningitidisremains 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 amongN. meningitidisisolates representative of major hyper-invasive lineages. In common with other meningococcal antigens, the genetic diversity ofhmbRresulted from a combination of intraspecies horizontal genetic exchange andde novomutation. Furthermore, genealogical analysis showed an association ofhmbRgenes with clonal complexes and the occurrence of twohmbRfamilies, 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.Keywords
This publication has 77 references indexed in Scilit:
- Epidemiological Evidence for the Role of the Hemoglobin Receptor, HmbR, in Meningococcal VirulenceThe Journal of Infectious Diseases, 2009
- Heme uptake across the outer membrane as revealed by crystal structures of the receptor–hemophore complexProceedings of the National Academy of Sciences of the United States of America, 2009
- Inference of Bacterial Microevolution Using Multilocus Sequence DataGenetics, 2007
- Opacity-Associated Adhesin Repertoire in Hyperinvasive Neisseria meningitidisInfection and Immunity, 2006
- Comparative structural analysis of TonB‐dependent outer membrane transporters: Implications for the transport cycleProteins-Structure Function and Bioinformatics, 2005
- Bayes Empirical Bayes Inference of Amino Acid Sites Under Positive SelectionMolecular Biology and Evolution, 2005
- Frequent False Detection of Positive Selection by the Likelihood Method with Branch-Site ModelsMolecular Biology and Evolution, 2004
- The maintenance of strain structure in populations of recombining infectious agentsNature Medicine, 1996
- CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choiceNucleic Acids Research, 1994
- The linear PCR reaction: a simple and robust method for sequencing amplified rRNA genesLetters in Applied Microbiology, 1991