1887

Abstract

can utilize haem, haemoglobin and haemoglobin–haptoglobin complexes as sources of iron via two TonB-dependent phase variable haemoglobin receptors, HmbR and HpuAB. HmbR is over-represented in disease isolates, suggesting a link between haemoglobin acquisition and meningococcal disease. This study compared the distribution of HpuAB and phase variation (PV) status of both receptors in disease and carriage isolates. Meningococcal disease ( = 214) and carriage ( = 305) isolates representative of multiple clonal complexes (CCs) were investigated for the distribution, polyG tract lengths and ON/OFF status of both haemoglobin receptors, and for the deletion mechanism for HpuAB. Strains with both receptors or only were present at similar frequencies among meningococcal disease isolates as compared with carriage isolates. However, >90 % of isolates from the three CCs CC5, CC8 and CC11 with the highest disease to carriage ratios contained both receptors. Strains with an -only phenotype were under-represented among disease isolates, suggesting selection against this receptor during systemic disease, possibly due to the receptor having a high level of immunogenicity or being inefficient in acquisition of iron during systemic spread. Absence of resulted from either complete deletion or replacement by an insertion element. In an examination of PV status, one or both receptors were found in an ON state in 91 % of disease and 71 % of carriage isolates. We suggest that expression of a haemoglobin receptor, either HmbR or HpuAB, is of major importance for systemic spread of meningococci, and that the presence of both receptors contributes to virulence in some strains.

Funding
This study was supported by the:
  • Higher Education Commission of Pakistan
  • Research Councils UK
  • RCUK
  • University of Leicester
  • University of Nottingham
  • University of Oxford
  • Wellcome Trust
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2011-05-01
2024-03-28
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References

  1. Bayliss C. D., Hoe J. C., Makepeace K., Martin P., Hood D. W., Moxon E. R. ( 2008). Neisseria meningitidis escape from the bactericidal activity of a monoclonal antibody is mediated by phase variation of lgtG and enhanced by a mutator phenotype. Infect Immun 76:5038–5048 [View Article][PubMed]
    [Google Scholar]
  2. Bidmos F. A., Neal K. R., Oldfield N. J., Turner D. P., Ala’aldeen D. A., Bayliss C. D. ( 2011). Persistence, replacement and rapid clonal expansion of meningococcal carriage isolates in a 2008 university student cohort. J Clin Microbiol 49:506–512[PubMed] [CrossRef]
    [Google Scholar]
  3. Boulton I. C., Gorringe A. R., Allison N., Robinson A., Gorinsky B., Joannou C. L., Evans R. W. ( 1998). Transferrin-binding protein B isolated from Neisseria meningitidis discriminates between apo and diferric human transferrin. Biochem J 334:269–273[PubMed]
    [Google Scholar]
  4. Caugant D. A., Maiden M. C. ( 2009). Meningococcal carriage and disease – population biology and evolution. Vaccine 27:Suppl. 2B64–B70 [View Article][PubMed]
    [Google Scholar]
  5. Claus H., Vogel U., Mühlenhoff M., Gerardy-Schahn R., Frosch M. ( 1997). Molecular divergence of the sia locus in different serogroups of Neisseria meningitidis expressing polysialic acid capsules. Mol Gen Genet 257:28–34 [View Article][PubMed]
    [Google Scholar]
  6. De Bolle X., Bayliss C. D., Field D., van de Ven T., Saunders N. J., Hood D. W., Moxon E. R. ( 2000). The length of a tetranucleotide repeat tract in Haemophilus influenzae determines the phase variation rate of a gene with homology to type III DNA methyltransferases. Mol Microbiol 35:211–222 [View Article][PubMed]
    [Google Scholar]
  7. Evans N. J., Harrison O. B., Clow K., Derrick J. P., Feavers I. M., Maiden M. C. ( 2010). Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor. Microbiology 156:1384–1393 [View Article][PubMed]
    [Google Scholar]
  8. Harrison O. B., Evans N. J., Blair J. M., Grimes H. S., Tinsley C. R., Nassif X., Kriz P., Ure R., Gray S. J. et al. ( 2009). Epidemiological evidence for the role of the hemoglobin receptor, HmbR, in meningococcal virulence. J Infect Dis 200:94–98 [View Article][PubMed]
    [Google Scholar]
  9. Jolley K. A., Kalmusova J., Feil E. J., Gupta S., Musilek M., Kriz P., Maiden M. C. ( 2000). Carried meningococci in the Czech Republic: a diverse recombining population. J Clin Microbiol 38:4492–4498[PubMed]
    [Google Scholar]
  10. Jordan P. W., Saunders N. J. ( 2009). Host iron binding proteins acting as niche indicators for Neisseria meningitidis . PLoS ONE 4:e5198 [View Article][PubMed]
    [Google Scholar]
  11. Lewis L. A., Dyer D. W. ( 1995). Identification of an iron-regulated outer membrane protein of Neisseria meningitidis involved in the utilization of hemoglobin complexed to haptoglobin. J Bacteriol 177:1299–1306[PubMed]
    [Google Scholar]
  12. Lewis L. A., Gipson M., Hartman K., Ownbey T., Vaughn J., Dyer D. W. ( 1999). Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2. Mol Microbiol 32:977–989 [View Article][PubMed]
    [Google Scholar]
  13. Maiden M. C., Bygraves J. A., Feil E., Morelli G., Russell J. E., Urwin R., Zhang Q., Zhou J., Zurth K. et al. ( 1998). Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 95:3140–3145 [View Article][PubMed]
    [Google Scholar]
  14. Maiden M. C. J., Stuart J. M., The UK Meningococcal Carriage Group. ( 2002). Carriage of serogroup C meningococci 1 year after meningococcal C conjugate polysaccharide vaccination. Lancet 359:1829–1830 [View Article][PubMed]
    [Google Scholar]
  15. Marsh J. W., O’Leary M. M., Shutt K. A., Harrison L. H. ( 2007). Deletion of fetA gene sequences in serogroup B and C Neisseria meningitidis isolates. J Clin Microbiol 45:1333–1335 [View Article][PubMed]
    [Google Scholar]
  16. Martin P., Sun L., Hood D. W., Moxon E. R. ( 2004). Involvement of genes of genome maintenance in the regulation of phase variation frequencies in Neisseria meningitidis . Microbiology 150:3001–3012 [View Article][PubMed]
    [Google Scholar]
  17. Moxon R., Bayliss C. D., Hood D. W. ( 2006). Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu Rev Genet 40:307–333 [View Article][PubMed]
    [Google Scholar]
  18. Otto B. R., Verweij-van Vught A. M., MacLaren D. M. ( 1992). Transferrins and heme-compounds as iron sources for pathogenic bacteria. Crit Rev Microbiol 18:217–233 [View Article][PubMed]
    [Google Scholar]
  19. Perkins-Balding D., Baer M. T., Stojiljkovic I. ( 2003). Identification of functionally important regions of a haemoglobin receptor from Neisseria meningitidis . Microbiology 149:3423–3435 [View Article][PubMed]
    [Google Scholar]
  20. Perkins-Balding D., Ratliff-Griffin M., Stojiljkovic I. ( 2004). Iron transport systems in Neisseria meningitidis. . Microbiol Mol Biol Rev 68:154–171 [View Article][PubMed]
    [Google Scholar]
  21. Pollard A. J. ( 2004). Global epidemiology of meningococcal disease and vaccine efficacy. Pediatr Infect Dis J 23:Suppl. 12S274–S279[PubMed]
    [Google Scholar]
  22. Richardson A. R., Stojiljkovic I. ( 1999). HmbR, a hemoglobin-binding outer membrane protein of Neisseria meningitidis, undergoes phase variation. J Bacteriol 181:2067–2074[PubMed]
    [Google Scholar]
  23. Richardson A. R., Yu Z., Popovic T., Stojiljkovic I. ( 2002). Mutator clones of Neisseria meningitidis in epidemic serogroup A disease. Proc Natl Acad Sci U S A 99:6103–6107 [View Article][PubMed]
    [Google Scholar]
  24. Rohde K. H., Dyer D. W. ( 2004). Analysis of haptoglobin and hemoglobin-haptoglobin interactions with the Neisseria meningitidis TonB-dependent receptor HpuAB by flow cytometry. Infect Immun 72:2494–2506 [View Article][PubMed]
    [Google Scholar]
  25. Russell J. E., Jolley K. A., Feavers I. M., Maiden M. C., Suker J. ( 2004). PorA variable regions of Neisseria meningitidis . Emerg Infect Dis 10:674–678[PubMed]
    [Google Scholar]
  26. Stephens D. S. ( 2007). Conquering the meningococcus. FEMS Microbiol Rev 31:3–14 [View Article][PubMed]
    [Google Scholar]
  27. Thompson E. A., Feavers I. M., Maiden M. C. ( 2003). Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component. Microbiology 149:1849–1858 [View Article][PubMed]
    [Google Scholar]
  28. van der Ende A., Hopman C. T., Dankert J. ( 1999). Deletion of porA by recombination between clusters of repetitive extragenic palindromic sequences in Neisseria meningitidis . Infect Immun 67:2928–2934[PubMed]
    [Google Scholar]
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