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Microbial Genomics logo Microbial Genomics

Volume 10, Issue 5

Development of a sequence-based OspA typing method for Open Access

Abstract

Lyme disease (LD), caused by spirochete bacteria of the genus , remains the most common vector-borne disease in the northern hemisphere. outer surface protein A (OspA) is an integral surface protein expressed during the tick cycle, and a validated vaccine target. There are at least 20 recognized genospecies, that vary in OspA serotype. This study presents a new sequence-based method for OspA typing using next-generation sequence data. Using a compiled database of over 400 genomes encompassing the 4 most common disease-causing genospecies, we characterized OspA diversity in a manner that can accommodate existing and new OspA types and then defined boundaries for classification and assignment of OspA types based on the sequence similarity. To accommodate potential novel OspA types, we have developed a new nomenclature: OspA type (IST). Beyond the ISTs that corresponded to existing OspA serotypes 1–8, we identified nine additional ISTs that cover new OspA variants in (IST9–10), (IST11–12), and other genospecies (IST13–17). The IST typing scheme and associated OspA variants are available as part of the PubMLST spp. database. Compared to traditional OspA serotyping methods, this new computational pipeline provides a more comprehensive and broadly applicable approach for characterization of OspA type and genospecies to support vaccine development.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Borrelia genospecies , in silico OspA typing and OspA diversity
Funding
This study was supported by the:
  • Pfizer
    • Principle Award Recipient: NotApplicable
© 2024 Pfizer Inc. - Richard A. Friedman, Assistant General Counsel for Pfizer In.c
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-05-24
2025-05-20
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References

  1. Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet 2012; 379:461–473 [View Article] [PubMed]
     [Google Scholar]
  2. Steere AC, Franc S, Wormser GP, Hu LT, Branda JA et al. Correction: Lyme borreliosis. Nat Rev Dis Primers 2017; 3:17062 [View Article] [PubMed]
     [Google Scholar]
  3. Stanek G, Strle F. Lyme borreliosis-from tick bite to diagnosis and treatment. FEMS Microbiol Rev 2018; 42:233–258 [View Article] [PubMed]
     [Google Scholar]
  4. Eisen RJ, Eisen L, Beard CB. County-scale distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the continental United States. J Med Entomol 2016; 53:349–386 [View Article] [PubMed]
     [Google Scholar]
  5. Margos G, Fingerle V, Reynolds S. Borrelia bavariensis: vector switch, niche invasion, and geographical spread of a tick-borne bacterial parasite. Front Ecol Evol 2019; 7: [View Article]
     [Google Scholar]
  6. Wolcott KA, Margos G, Fingerle V, Becker NS. Host association of Borrelia burgdorferi sensu lato: a review. Ticks Tick Borne Dis 2021; 12:101766 [View Article] [PubMed]
     [Google Scholar]
  7. Schwartz AM, Hinckley AF, Mead PS, Hook SA, Kugeler KJ. Surveillance for Lyme disease - United States, 2008-2015. MMWR Surveill Summ 2017; 66:1–12 [View Article] [PubMed]
     [Google Scholar]
  8. Kugeler KJ, Schwartz AM, Delorey MJ, Mead PS, Hinckley AF. Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018. Emerg Infect Dis 2021; 27:616–619 [View Article] [PubMed]
     [Google Scholar]
  9. Müller I, Freitag MH, Poggensee G, Scharnetzky E, Straube E et al. Evaluating frequency, diagnostic quality, and cost of Lyme borreliosis testing in Germany: a retrospective model analysis. Clin Dev Immunol 2012; 2012:595427 [View Article] [PubMed]
     [Google Scholar]
  10. Eisen RJ, Eisen L. The blacklegged tick, Ixodes scapularis: an increasing public health concern. Trends Parasitol 2018; 34:295–309 [View Article] [PubMed]
     [Google Scholar]
  11. Eisen RJ, Eisen L, Ogden NH, Beard CB. Linkages of weather and climate with Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae), enzootic transmission of Borrelia burgdorferi, and Lyme disease in North America. J Med Entomol 2016; 53:250–261 [View Article] [PubMed]
     [Google Scholar]
  12. Hahn MB, Jarnevich CS, Monaghan AJ, Eisen RJ. Modeling the geographic distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the contiguous United States. J Med Entomol 2016; 53:1176–1191 [View Article] [PubMed]
     [Google Scholar]
  13. Gasmi S, Ogden NH, Leighton PA, Lindsay LR, Thivierge K. Analysis of the human population bitten by Ixodes scapularis ticks in Quebec, Canada: increasing risk of Lyme disease. Ticks Tick Borne Dis 2016; 7:1075–1081 [View Article] [PubMed]
     [Google Scholar]
  14. Yang XF, Pal U, Alani SM, Fikrig E, Norgard MV. Essential role for OspA/B in the life cycle of the Lyme disease spirochete. J Exp Med 2004; 199:641–648 [View Article] [PubMed]
     [Google Scholar]
  15. Comstedt P, Schüler W, Meinke A, Lundberg U. The novel Lyme borreliosis vaccine VLA15 shows broad protection against Borrelia species expressing six different OspA serotypes. PLoS One 2017; 12:e0184357 [View Article] [PubMed]
     [Google Scholar]
  16. Comstedt P, Hanner M, Schüler W, Meinke A, Lundberg U. Design and development of a novel vaccine for protection against Lyme borreliosis. PLoS One 2014; 9:e113294 [View Article] [PubMed]
     [Google Scholar]
  17. Koide S, Yang X, Huang X, Dunn JJ, Luft BJ. Structure-based design of a second-generation Lyme disease vaccine based on a C-terminal fragment of Borrelia burgdorferi OspA. J Mol Biol 2005; 350:290–299 [View Article] [PubMed]
     [Google Scholar]
  18. Willett TA, Meyer AL, Brown EL, Huber BT. An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope. Proc Natl Acad Sci U S A 2004; 101:1303–1308 [View Article] [PubMed]
     [Google Scholar]
  19. Sigal LH, Zahradnik JM, Lavin P, Patella SJ, Bryant G et al. A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant outer-surface protein A Lyme Disease vaccine study consortium. N Engl J Med 1998; 339:216–222 [View Article] [PubMed]
     [Google Scholar]
  20. Steere AC, Sikand VK, Meurice F, Parenti DL, Fikrig E et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease vaccine study group. N Engl J Med 1998; 339:209–215 [View Article] [PubMed]
     [Google Scholar]
  21. Nayak A, Schüler W, Seidel S, Gomez I, Meinke A et al. Broadly protective multivalent OspA vaccine against Lyme borreliosis, developed based on surface shaping of the C-terminal fragment. Infect Immun 2020; 88:e00917-19 [View Article] [PubMed]
     [Google Scholar]
  22. Piesman J, Gern L. Lyme borreliosis in Europe and North America. Parasitology 2004; 129 Suppl:S191–220 [View Article] [PubMed]
     [Google Scholar]
  23. Will G, Jauris-Heipke S, Schwab E, Busch U, Rössler D et al. Sequence analysis of ospA genes shows homogeneity within Borrelia burgdorferi sensu stricto and Borrelia afzelii strains but reveals major subgroups within the Borrelia garinii species. Med Microbiol Immunol 1995; 184:73–80 [View Article] [PubMed]
     [Google Scholar]
  24. Margos G, Vollmer SA, Cornet M, Garnier M, Fingerle V et al. A new Borrelia species defined by multilocus sequence analysis of housekeeping genes. Appl Environ Microbiol 2009; 75:5410–5416 [View Article] [PubMed]
     [Google Scholar]
  25. Wilske B, Preac-Mursic V, Göbel UB, Graf B, Jauris S et al. An OspA serotyping system for Borrelia burgdorferi based on reactivity with monoclonal antibodies and OspA sequence analysis. J Clin Microbiol 1993; 31:340–350 [View Article] [PubMed]
     [Google Scholar]
  26. Wilske B, Busch U, Eiffert H, Fingerle V, Pfister HW et al. Diversity of OspA and OspC among cerebrospinal fluid isolates of Borrelia burgdorferi sensu lato from patients with neuroborreliosis in Germany. Med Microbiol Immunol 1996; 184:195–201 [View Article] [PubMed]
     [Google Scholar]
  27. Wang G, Liveris D, Mukherjee P, Jungnick S, Margos G et al. Molecular typing of Borrelia burgdorferi. Curr Protoc Microbiol 2014; 34:12C [View Article] [PubMed]
     [Google Scholar]
  28. Wang G, van Dam AP, Schwartz I, Dankert J. Molecular typing of Borrelia burgdorferi sensu lato: taxonomic, epidemiological, and clinical implications. Clin Microbiol Rev 1999; 12:633–653 [View Article] [PubMed]
     [Google Scholar]
  29. Fingerle V, Schulte-Spechtel UC, Ruzic-Sabljic E, Leonhard S, Hofmann H et al. Epidemiological aspects and molecular characterization of Borrelia burgdorferi s.l. from southern Germany with special respect to the new species Borrelia spielmanii sp. nov. Int J Med Microbiol 2008; 298:279–290 [View Article] [PubMed]
     [Google Scholar]
  30. Michel H, Wilske B, Hettche G, Göttner G, Heimerl C et al. An ospA-polymerase chain reaction/restriction fragment length polymorphism-based method for sensitive detection and reliable differentiation of all European Borrelia burgdorferi sensu lato species and OspA types. Med Microbiol Immunol 2004; 193:219–226 [View Article] [PubMed]
     [Google Scholar]
  31. Schulte-Spechtel U, Fingerle V, Goettner G, Rogge S, Wilske B. Molecular analysis of decorin-binding protein A (DbpA) reveals five major groups among European Borrelia burgdorferi sensu lato strains with impact for the development of serological assays and indicates lateral gene transfer of the dbpA gene. Int J Med Microbiol 2006; 296 Suppl 40:250–266 [View Article] [PubMed]
     [Google Scholar]
  32. Margos G, Gatewood AG, Aanensen DM, Hanincová K, Terekhova D et al. MLST of housekeeping genes captures geographic population structure and suggests a European origin of Borrelia burgdorferi. Proc Natl Acad Sci U S A 2008; 105:8730–8735 [View Article] [PubMed]
     [Google Scholar]
  33. Coipan EC, Fonville M, Tijsse-Klasen E, van der Giessen JWB, Takken W et al. Geodemographic analysis of Borrelia burgdorferi sensu lato using the 5S-23S rDNA spacer region. Infect Genet Evol 2013; 17:216–222 [View Article] [PubMed]
     [Google Scholar]
  34. Schwartz I, Margos G, Casjens SR, Qiu W-G, Eggers CH. Multipartite genome of Lyme disease Borrelia: structure, variation and prophages. Curr Issues Mol Biol 2021; 42:409–454 [View Article] [PubMed]
     [Google Scholar]
  35. Jolley KA, Bray JE, Maiden MCJ. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res 2018; 3:124 [View Article] [PubMed]
     [Google Scholar]
  36. Wagemakers A, Oei A, Fikrig MM, Miellet WR, Hovius JW. The relapsing fever spirochete Borrelia miyamotoi is cultivable in a modified Kelly-Pettenkofer medium, and is resistant to human complement. Parasit Vectors 2014; 7:418 [View Article] [PubMed]
     [Google Scholar]
  37. Jones CH, Mohamed N, Rojas E, Andrew L, Hoyos J et al. Comparison of phenotypic and genotypic approaches to capsule typing of Neisseria meningitidis by use of invasive and carriage isolate collections. J Clin Microbiol 2016; 54:25–34 [View Article] [PubMed]
     [Google Scholar]
  38. Treangen TJ, Ondov BD, Koren S, Phillippy AM. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 2014; 15:524 [View Article] [PubMed]
     [Google Scholar]
  39. Tamura K, Stecher G, Kumar S. MEGA11: molecular evolutionary genetics analysis version 11. Mol Biol Evol 2021; 38:3022–3027 [View Article] [PubMed]
     [Google Scholar]
  40. Nakamura T, Yamada KD, Tomii K, Katoh K. Parallelization of MAFFT for large-scale multiple sequence alignments. Bioinformatics 2018; 34:2490–2492 [View Article] [PubMed]
     [Google Scholar]
  41. Pfizer Pfizer and Valneva Initiate Phase 3 Study of Lyme Disease Vaccine Candidate VLA15: Pfizer; 2022. n.d https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-valneva-initiate-phase-3-study-lyme-disease
  42. Marconi RT, Hohenberger S, Jauris-Heipke S, Schulte-Spechtel U, LaVoie CP et al. Genetic analysis of Borrelia garinii OspA serotype 4 strains associated with neuroborreliosis: evidence for extensive genetic homogeneity. J Clin Microbiol 1999; 37:3965–3970 [View Article] [PubMed]
     [Google Scholar]
  43. Gatzmann F, Metzler D, Krebs S, Blum H, Sing A et al. NGS population genetics analyses reveal divergent evolution of a Lyme Borreliosis agent in Europe and Asia. Ticks Tick Borne Dis 2015; 6:344–351 [View Article] [PubMed]
     [Google Scholar]
  44. Margos G, Wilske B, Sing A, Hizo-Teufel C, Cao W-C et al. Borrelia bavariensis sp. nov. is widely distributed in Europe and Asia. Int J Syst Evol Microbiol 2013; 63:4284–4288 [View Article] [PubMed]
     [Google Scholar]
  45. Wilske B, Busch U, Fingerle V, Jauris-Heipke S, Preac Mursic V et al. Immunological and molecular variability of OspA and OspC. Implications for Borrelia vaccine development. Infection 1996; 24:208–212 [View Article] [PubMed]
     [Google Scholar]
  46. Wang G, van Dam AP, Spanjaard L, Dankert J. Molecular typing of Borrelia burgdorferi sensu lato by randomly amplified polymorphic DNA fingerprinting analysis. J Clin Microbiol 1998; 36:768–776 [View Article] [PubMed]
     [Google Scholar]
  47. Wang J, Masuzawa T, Yanagihara Y. Characterization of Borrelia garinii isolated from Lyme disease patients in Hokkaido, Japan, by sequence analysis of OspA and OspB genes. FEMS Microbiol Lett 1997; 154:371–375 [View Article] [PubMed]
     [Google Scholar]
  48. Grego E, Bertolotti L, Peletto S, Amore G, Tomassone L et al. Borrelia lusitaniae OspA gene heterogeneity in Mediterranean basin area. J Mol Evol 2007; 65:512–518 [View Article] [PubMed]
     [Google Scholar]
  49. Masuzawa T, Wilske B, Komikado T, Suzuki H, Kawabata H et al. Comparison of OspA serotypes for Borrelia burgdorferi sensu lato from Japan, Europe and North America. Microbiol Immunol 1996; 40:539–545 [View Article] [PubMed]
     [Google Scholar]
  50. Wang G, van Dam AP, Dankert J. Two distinct ospA genes among Borrelia valaisiana strains. Res Microbiol 2000; 151:325–331 [View Article] [PubMed]
     [Google Scholar]
  51. Pritt BS, Mead PS, Johnson DKH, Neitzel DF, Respicio-Kingry LB et al. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis 2016; 16:556–564 [View Article] [PubMed]
     [Google Scholar]
  52. Rauter C, Hartung T. Prevalence of Borrelia burgdorferi sensu lato genospecies in Ixodes ricinus ticks in Europe: a metaanalysis. Appl Environ Microbiol 2005; 71:7203–7216 [View Article] [PubMed]
     [Google Scholar]
  53. Wang G, van Dam AP, Dankert J. Evidence for frequent OspC gene transfer between Borrelia valaisiana sp. nov. and other Lyme disease spirochetes. FEMS Microbiol Lett 1999; 177:289–296 [View Article] [PubMed]
     [Google Scholar]
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Development of a sequence-based in silico OspA typing method for Borrelia burgdorferi sensu lato
M Gen 10, 001252 (2024); https://doi.org/10.1099/mgen.0.001252
/content/journal/mgen/10.1099/mgen.0.001252
/content/journal/mgen/10.1099/mgen.0.001252
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