1887

Abstract

Factor H binding protein (fHbp) is a major antigenic component of novel vaccines designed to protect against meningococcal disease. Prediction of the potential coverage of these vaccines is difficult, as fHbp is antigenically variable and levels of expression differ among isolates. Transcriptional regulation of the gene is poorly understood, although evidence suggests that oxygen availability is involved. In this study iron accessibility was found to affect transcription. However, regulation differed among meningococcal clonal complexes (ccs). For the majority of isolates, increased iron concentrations upregulated transcription. This effect was enhanced by the presence of a 181 bp insertion element upstream of , associated with isolates belonging to cc4 and cc5. Conversely, meningococci belonging to cc32 showed iron-repressed control of , as regulation was dominated by cotranscription with the iron-repressed upstream gene . These results highlight the complexity of regulation and demonstrate that control of transcription can vary among genetic lineages.

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2012-04-01
2019-10-19
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References

  1. Abe H. , Aiba H. . ( 1996; ). Differential contributions of two elements of rho-independent terminator to transcription termination and mRNA stabilization. . Biochimie 78:, 1035–1042. [CrossRef] [PubMed]
    [Google Scholar]
  2. Ambur O. H. , Frye S. A. , Tønjum T. . ( 2007; ). New functional identity for the DNA uptake sequence in transformation and its presence in transcriptional terminators. . J Bacteriol 189:, 2077–2085. [CrossRef] [PubMed]
    [Google Scholar]
  3. Bartolini E. , Frigimelica E. , Giovinazzi S. , Galli G. , Shaik Y. , Genco C. , Welsch J. A. , Granoff D. M. , Grandi G. , Grifantini R. . ( 2006; ). Role of FNR and FNR-regulated, sugar fermentation genes in Neisseria meningitidis infection. . Mol Microbiol 60:, 963–972. [CrossRef] [PubMed]
    [Google Scholar]
  4. Borrow R. , Carlone G. M. , Rosenstein N. , Blake M. , Feavers I. , Martin D. , Zollinger W. , Robbins J. , Aaberge I. . & other authors ( 2006; ). Neisseria meningitidis group B correlates of protection and assay standardization–international meeting report Emory University, Atlanta, Georgia, United States, 16–17 March 2005. . Vaccine 24:, 5093–5107. [CrossRef] [PubMed]
    [Google Scholar]
  5. Bullen J. J. , Spalding P. B. , Ward C. G. , Rogers H. J. . ( 1992; ). The role of Eh, pH and iron in the bactericidal power of human plasma. . FEMS Microbiol Lett 94:, 47–52. [CrossRef] [PubMed]
    [Google Scholar]
  6. Cantini F. , Savino S. , Scarselli M. , Masignani V. , Pizza M. , Romagnoli G. , Swennen E. , Veggi D. , Banci L. , Rappuoli R. . ( 2006; ). Solution structure of the immunodominant domain of protective antigen GNA1870 of Neisseria meningitidis . . J Biol Chem 281:, 7220–7227. [CrossRef] [PubMed]
    [Google Scholar]
  7. Crack J. , Green J. , Thomson A. J. . ( 2004; ). Mechanism of oxygen sensing by the bacterial transcription factor fumarate-nitrate reduction (FNR). . J Biol Chem 279:, 9278–9286. [CrossRef] [PubMed]
    [Google Scholar]
  8. Didelot X. , Urwin R. , Maiden M. C. J. , Falush D. . ( 2009; ). Genealogical typing of Neisseria meningitidis . . Microbiology 155:, 3176–3186. [CrossRef] [PubMed]
    [Google Scholar]
  9. Donnelly J. , Medini D. , Boccadifuoco G. , Biolchi A. , Ward J. , Frasch C. , Moxon E. R. , Stella M. , Comanducci M. . & other authors ( 2010; ). Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines. . Proc Natl Acad Sci U S A 107:, 19490–19495. [CrossRef] [PubMed]
    [Google Scholar]
  10. Edwards J. , Cole L. J. , Green J. B. , Thomson M. J. , Wood A. J. , Whittingham J. L. , Moir J. W. B. . ( 2010; ). Binding to DNA protects Neisseria meningitidis fumarate and nitrate reductase regulator (FNR) from oxygen. . J Biol Chem 285:, 1105–1112. [CrossRef] [PubMed]
    [Google Scholar]
  11. Feavers I. M. . ( 2000; ). Bacterial genomics: ABC of meningococcal diversity. . Nature 404:, 451–452. [CrossRef] [PubMed]
    [Google Scholar]
  12. Findlow J. , Borrow R. , Snape M. D. , Dawson T. , Holland A. , John T. M. , Evans A. , Telford K.-L. , Ypma E. . & other authors ( 2010; ). Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant meningococcal serogroup B vaccine with and without outer membrane vesicles, administered in infancy. . Clin Infect Dis 51:, 1127–1137. [CrossRef] [PubMed]
    [Google Scholar]
  13. Genco C. A. , Desai P. J. . ( 1996; ). Iron acquisition in the pathogenic Neisseria . . Trends Microbiol 4:, 179–184. [CrossRef] [PubMed]
    [Google Scholar]
  14. Giuliani M. M. , Biolchi A. , Serruto D. , Ferlicca F. , Vienken K. , Oster P. , Rappuoli R. , Pizza M. , Donnelly J. . ( 2010; ). Measuring antigen-specific bactericidal responses to a multicomponent vaccine against serogroup B meningococcus. . Vaccine 28:, 5023–5030. [CrossRef] [PubMed]
    [Google Scholar]
  15. Grifantini R. , Sebastian S. , Frigimelica E. , Draghi M. , Bartolini E. , Muzzi A. , Rappuoli R. , Grandi G. , Genco C. A. . ( 2003; ). Identification of iron-activated and -repressed Fur-dependent genes by transcriptome analysis of Neisseria meningitidis group B. . Proc Natl Acad Sci U S A 100:, 9542–9547. [CrossRef] [PubMed]
    [Google Scholar]
  16. Halperin S. A. , Gupta A. , Jeanfreau R. , Klein N. , Reisinger K. , Walter E. , McCarthy M. , Karsten A. , Bedell L. . & other authors ( 2010; ). Clinical Immunogenicity and Safety Profile of Two Quadrivalent Meningococcal Conjugate Vaccines in 2907 2-to-10-year-old Children. . Presented at 17th International Pathogenic Neisseria Conference, 11–16 September, 2010, Banff, AB, Canada.
    [Google Scholar]
  17. Jacobsson S. , Hedberg S. T. , Mölling P. , Unemo M. , Comanducci M. , Rappuoli R. , Olcén P. . ( 2009; ). Prevalence and sequence variations of the genes encoding the five antigens included in the novel 5CVMB vaccine covering group B meningococcal disease. . Vaccine 27:, 1579–1584. [CrossRef] [PubMed]
    [Google Scholar]
  18. Jiang H. Q. , Hoiseth S. K. , Harris S. L. , McNeil L. K. , Zhu D. Z. , Tan C. W. , Scott A. A. , Alexander K. , Mason K. . & other authors ( 2010; ). Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease. . Vaccine 28:, 6086–6093. [CrossRef] [PubMed]
    [Google Scholar]
  19. Jolley K. A. , Maiden M. C. J. . ( 2010; ). BIGSdb: scalable analysis of bacterial genome variation at the population level. . BMC Bioinformatics 11:, 595. [CrossRef] [PubMed]
    [Google Scholar]
  20. Jolley K. A. , Brehony C. , Maiden M. C. J. . ( 2007; ). Molecular typing of meningococci: recommendations for target choice and nomenclature. . FEMS Microbiol Rev 31:, 89–96. [CrossRef] [PubMed]
    [Google Scholar]
  21. Kingsford C. L. , Ayanbule K. , Salzberg S. L. . ( 2007; ). Rapid, accurate, computational discovery of Rho-independent transcription terminators illuminates their relationship to DNA uptake. . Genome Biol 8:, R22. [CrossRef] [PubMed]
    [Google Scholar]
  22. Koeberling O. , Delany I. , Granoff D. M. . ( 2011; ). A critical threshold of meningococcal factor H binding protein expression is required for increased breadth of protective antibodies elicited by native outer membrane vesicle vaccines. . Clin Vaccine Immunol 18:, 736–742. [CrossRef] [PubMed]
    [Google Scholar]
  23. Madico G. , Welsch J. A. , Lewis L. A. , McNaughton A. , Perlman D. H. , Costello C. E. , Ngampasutadol J. , Vogel U. , Granoff D. M. , Ram S. . ( 2006; ). The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. . J Immunol 177:, 501–510.[PubMed] [CrossRef]
    [Google Scholar]
  24. Maiden M. C. J. , Bygraves J. A. , Feil E. , Morelli G. , Russell J. E. , Urwin R. , Zhang Q. , Zhou J. J. , Zurth K. . & other authors ( 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. [CrossRef] [PubMed]
    [Google Scholar]
  25. Masignani V. , Comanducci M. , Giuliani M. M. , Bambini S. , Adu-Bobie J. , Arico B. , Brunelli B. , Pieri A. , Santini L. . & other authors ( 2003; ). Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. . J Exp Med 197:, 789–799. [CrossRef] [PubMed]
    [Google Scholar]
  26. Maslanka S. E. , Gheesling L. L. , Libutti D. E. , Donaldson K. B. J. , Harakeh H. S. , Dykes J. K. , Arhin F. F. , Devi S. J. N. , Frasch C. E. . & other authors ( 1997; ). Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. . Clin Diagn Lab Immunol 4:, 156–167.[PubMed]
    [Google Scholar]
  27. Oriente F. , Scarlato V. , Delany I. . ( 2010; ). Expression of factor H binding protein of meningococcus responds to oxygen limitation through a dedicated FNR-regulated promoter. . J Bacteriol 192:, 691–701. [CrossRef] [PubMed]
    [Google Scholar]
  28. Perkins-Balding D. , Ratliff-Griffin M. , Stojiljkovic I. . ( 2004; ). Iron transport systems in Neisseria meningitidis . . Microbiol Mol Biol Rev 68:, 154–171. [CrossRef] [PubMed]
    [Google Scholar]
  29. Rappuoli R. . ( 2010; ). Meningococcal Biology and Vaccines: ten Years of Genomics and Reverse Vaccinology. . Presented at 17th International Pathogenic Neisseria Conference, 11–16 September, 2010, Banff, AB, Canada.
    [Google Scholar]
  30. Seib K. L. , Serruto D. , Oriente F. , Delany I. , Adu-Bobie J. , Veggi D. , Aricò B. , Rappuoli R. , Pizza M. . ( 2009; ). Factor H-binding protein is important for meningococcal survival in human whole blood and serum and in the presence of the antimicrobial peptide LL-37. . Infect Immun 77:, 292–299. [CrossRef] [PubMed]
    [Google Scholar]
  31. Seib K. L. , Oriente F. , Adu-Bobie J. , Montanari P. , Ferlicca F. , Giuliani M. M. , Rappuoli R. , Pizza M. , Delany I. . ( 2010; ). Influence of serogroup B meningococcal vaccine antigens on growth and survival of the meningococcus in vitro and in ex vivo and in vivo models of infection. . Vaccine 28:, 2416–2427. [CrossRef] [PubMed]
    [Google Scholar]
  32. Seib K. L. , Brunelli B. , Brogioni B. , Palumbo E. , Bambini S. , Muzzi A. , DiMarcello F. , Marchi S. , van der Ende A. . & other authors ( 2011; ). Characterization of diverse subvariants of the meningococcal factor H (fH) binding protein for their ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies. . Infect Immun 79:, 970–981. [CrossRef] [PubMed]
    [Google Scholar]
  33. Snape M. D. , Pollard A. J. . ( 2005; ). Meningococcal polysaccharide-protein conjugate vaccines. . Lancet Infect Dis 5:, 21–30. [CrossRef] [PubMed]
    [Google Scholar]
  34. Welsch J. A. , Ram S. , Koeberling O. , Granoff D. M. . ( 2008; ). Complement-dependent synergistic bactericidal activity of antibodies against factor H-binding protein, a sparsely distributed meningococcal vaccine antigen. . J Infect Dis 197:, 1053–1061. [CrossRef] [PubMed]
    [Google Scholar]
  35. Yongye A. B. , Gonzalez-Outeiriño J. , Glushka J. , Schultheis V. , Woods R. J. . ( 2008; ). The conformational properties of methyl α-(2,8)-di/trisialosides and their N-acyl analogues: implications for anti-Neisseria meningitidis B vaccine design. . Biochemistry 47:, 12493–12514. [CrossRef] [PubMed]
    [Google Scholar]
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