Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2017, Article ID 1436080, 12 pages
https://doi.org/10.1155/2017/1436080
Review Article

Novel Treponema pallidum Recombinant Antigens for Syphilis Diagnostics: Current Status and Future Prospects

Department of Laboratory Diagnostics of Sexually Transmitted Diseases and Dermatoses, State Research Center of Dermatovenereology and Cosmetology, Korolenko Street 3/6, Moscow 107076, Russia

Correspondence should be addressed to Dmitry Deryabin; ur.xednay@nibayredgd

Received 2 February 2017; Accepted 21 March 2017; Published 24 April 2017

Academic Editor: György Schneider

Copyright © 2017 Aleksey Kubanov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. J. Norris, D. L. Cox, and G. M. Weinstock, “Biology of Treponema pallidum: correlation of functional activities with genome sequence data,” Journal of Molecular Microbiology and Biotechnology, vol. 3, no. 1, pp. 37–62, 2001. View at Google Scholar · View at Scopus
  2. J. Liu, J. K. Howell, S. D. Bradley, Y. Zheng, Z. H. Zhou, and S. J. Norris, “Cellular architecture of Treponema pallidum: novel flagellum, periplasmic cone, and cell envelope as revealed by cryo electron tomography,” Journal of Molecular Biology, vol. 403, no. 4, pp. 546–561, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. R. E. LaFond and S. A. Lukehart, “Biological basis for syphilis,” Clinical Microbiology Reviews, vol. 19, no. 1, pp. 29–49, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. R. W. Peeling and E. W. Hook III, “The pathogenesis of syphilis: The Great Mimicker, revisited,” Journal of Pathology, vol. 208, no. 2, pp. 224–232, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. C. J. Mulligan, S. J. Norris, and S. A. Lukehart, “Molecular studies in Treponema pallidum evolution: toward clarity?” PLoS Neglected Tropical Diseases, vol. 2, no. 1, article e184, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. C. M. Fraser, S. J. Norris, G. M. Weinstock et al., “Complete genome sequence of Treponema pallidum, the syphilis spirochete,” Science, vol. 281, no. 5375, pp. 375–388, 1998. View at Publisher · View at Google Scholar · View at Scopus
  7. P. Matějková, M. Strouhal, D. Šmajs et al., “Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays,” BMC Microbiology, vol. 8, article 76, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. H. Pětrošová, P. Pospíšilová, M. Strouhal et al., “Resequencing of Treponema pallidumssp. pallidum strains Nichols and SS14: correction of sequencing errors resulted in increased separation of syphilis treponeme subclusters,” PLoS ONE, vol. 8, no. 9, Article ID e74319, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. A. A. T. Naqvi, M. Shahbaaz, F. Ahmad, and M. I. Hassan, “Identification of functional candidates amongst hypothetical proteins of Treponema pallidumssp. Pallidum,” PLoS ONE, vol. 10, no. 4, Article ID e0124177, 2015. View at Publisher · View at Google Scholar · View at Scopus
  10. S. J. Norris, G. M. Weinstock, and N. Steven J, “The genome sequence of Treponema pallidum, the syphilis spirochete: will clinicians benefit?” Current Opinion in Infectious Diseases, vol. 13, no. 1, pp. 29–36, 2000. View at Publisher · View at Google Scholar · View at Scopus
  11. S. J. Norris, “Polypeptides of Treponema pallidum: progress toward understanding their structural, functional, and immunologie roles,” Microbiological Reviews, vol. 57, no. 3, pp. 750–779, 1993. View at Google Scholar · View at Scopus
  12. M. A. McGill, D. G. Edmondson, J. A. Carroll, R. G. Cook, R. S. Orkiszewski, and S. J. Norris, “Characterization and serologic analysis of the Treponema pallidum proteome,” Infection and Immunity, vol. 78, no. 6, pp. 2631–2643, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. K. K. Osbak, S. Houston, K. V. Lithgow et al., “Characterizing the syphilis-causing Treponema pallidum ssp. pallidum proteome using complementary mass spectrometry,” PLoS Neglected Tropical Diseases, vol. 10, no. 9, Article ID e0004988, 2016. View at Publisher · View at Google Scholar
  14. D. L. Cox, A. Luthra, S. Dunham-Ems et al., “Surface immunolabeling and consensus computational framework to identify candidate rare outer membrane proteins of Treponema pallidum,” Infection and Immunity, vol. 78, no. 12, pp. 5178–5194, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Li, M. A. Motaleb, M. Sal, S. F. Goldstein, and N. W. Charon, “Spirochete piroplasmic flagella and motility,” Journal of Molecular Microbiology and Biotechnology, vol. 2, no. 4, pp. 345–354, 2000. View at Google Scholar · View at Scopus
  16. J. C. Setubal, M. Reis, J. Matsunaga, and D. A. Haake, “Lipoprotein computational prediction in spirochaetal genomes,” Microbiology, vol. 152, no. 1, pp. 113–121, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. M. B. Brinkman, M. McKevitt, M. McLoughlin et al., “Reactivity of antibodies from syphilis patients to a protein array representing the Treponema pallidum proteome,” Journal of Clinical Microbiology, vol. 44, no. 3, pp. 888–891, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. J. D. Radolf and D. C. Desrosiers, “Treponema pallidum, the stealth pathogen, changes, but how?: MicroCommentary,” Molecular Microbiology, vol. 72, no. 5, pp. 1081–1086, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. G. Hart, “Syphilis tests in diagnostic and therapeutic decision making,” Annals of Internal Medicine, vol. 104, no. 3, pp. 368–376, 1986. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Gerber, S. Krell, and J. Morenz, “Recombinant Treponema pallidum antigens in syphilis serology,” Immunobiology, vol. 196, no. 5, pp. 535–549, 1996. View at Google Scholar · View at Scopus
  21. M. J. Binnicker, D. J. Jespersen, and L. O. Rollins, “Treponema-specific tests for serodiagnosis of syphilis: comparative evaluation of seven assays,” Journal of Clinical Microbiology, vol. 49, no. 4, pp. 1313–1317, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. N. R. Chamberlain, M. E. Brandt, A. L. Erwin, J. D. Radolf, and M. V. Norgard, “Major integral membrane protein immunogens of Treponema pallidum are proteolipids,” Infection and Immunity, vol. 57, no. 9, pp. 2872–2877, 1989. View at Google Scholar · View at Scopus
  23. C. A. Brautigam, R. K. Deka, and M. V. Norgard, “Purification, crystallization and preliminary X-ray analysis of TP0435 (Tp17) from the syphilis spirochete Treponema pallidum,” Acta Crystallographica Section F: Structural Biology and Crystallization Communications, vol. 69, no. 4, pp. 453–455, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. C. A. Brautigam, R. K. Deka, W. Z. Liu, and M. V. Norgard, “Insights into the potential function and membrane organization of the TP0435 (Tp17) lipoprotein from Treponema pallidum derived from structural and biophysical analyses,” Protein Science, vol. 24, no. 1, pp. 11–19, 2015. View at Publisher · View at Google Scholar · View at Scopus
  25. R.-L. Zhang, Q.-Q. Wang, J.-P. Zhang, and L.-J. Yang, “Tp17 membrane protein of Treponema pallidum activates endothelial cells in vitro,” International Immunopharmacology, vol. 25, no. 2, pp. 538–544, 2016. View at Publisher · View at Google Scholar · View at Scopus
  26. R. K. Deka, M. Machius, M. V. Norgard, and D. R. Tomchick, “Crystal structure of the 47-kDa lipoprotein of Treponema pallidum reveals a novel penicillin-binding protein,” The Journal of Biological Chemistry, vol. 277, no. 44, pp. 41857–41864, 2002. View at Publisher · View at Google Scholar · View at Scopus
  27. K. H. Lee, H.-J. Choi, M.-G. Lee, and J. B. Lee, “Virulent Treponema pallidum 47 kDa antigen regulates the expression of cell adhesion molecules and binding of T-lymphocytes to cultured human dermal microvascular endothelial cells,” Yonsei Medical Journal, vol. 41, no. 5, pp. 623–633, 2000. View at Publisher · View at Google Scholar · View at Scopus
  28. J. L. Backhouse and S. I. Nesteroff, “Treponema pallidum western blot: comparison with the FTA-ABS test as a confirmatory test for syphilis,” Diagnostic Microbiology and Infectious Disease, vol. 39, no. 1, pp. 9–14, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. V. Sambri, A. Marangoni, M. A. Simone, A. D'Antuono, M. Negosanti, and R. Cevenini, “Evaluation of recomWell Treponema, a novel recombinant antigen-based enzyme-linked immunosorbent assay for the diagnosis of syphilis,” Clinical Microbiology and Infection, vol. 7, no. 4, pp. 200–205, 2001. View at Publisher · View at Google Scholar · View at Scopus
  30. A. H. Sun, Y. F. Mao, Y. Hu, Q. Sun, and J. Yan, “Sensitive and specific ELISA coated by TpN15-TpN17-TpN47 fusion protein for detection of antibodies to Treponema pallidum,” Clinical Chemistry and Laboratory Medicine, vol. 47, no. 3, pp. 321–326, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. N.-L. Huang, L. Ye, M. E. Schneider et al., “Development of a novel protein biochip enabling validation of immunological assays and detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis,” Biosensors and Bioelectronics, vol. 75, pp. 465–471, 2016. View at Publisher · View at Google Scholar · View at Scopus
  32. O. E. IJsselmuiden, L. M. Schouls, E. Stolz et al., “Sensitivity and specificity of an enzyme-linked immunosorbent assay using the recombinant DNA-derived Treponema pallidum protein TmpA for serodiagnosis of syphilis and the potential use of TmpA for assessing the effect of antibiotic therapy,” Journal of Clinical Microbiology, vol. 27, no. 1, pp. 152–157, 1989. View at Google Scholar · View at Scopus
  33. R. K. Deka, C. A. Brautigam, X. F. Yang et al., “The PnrA (Tp0319; TmpC) lipoprotein represents a new family of bacterial purine nucleoside receptor encoded within an ATP-binding cassette (ABC)-like operon in Treponema pallidum,” Journal of Biological Chemistry, vol. 281, no. 12, pp. 8072–8081, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. R. K. Deka, M. S. Goldberg, K. E. Hagman, and M. V. Norgard, “The Tp38 (TpMglB-2) lipoprotein binds glucose in a manner consistent with receptor function in Treponema pallidum,” Journal of Bacteriology, vol. 186, no. 8, pp. 2303–2308, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. J. Xiao, G. Guo, and M. Zeng, “Gene cloning and expression of outer membrane protein TP0684 of Treponema pallidum,” Chinese Journal of Biologicals, vol. 20, no. 4, pp. 248–251, 2007. View at Google Scholar · View at Scopus
  36. Y. Xiao, N. Wu, S. Liu, F. Zhao, and Y. Wu, “Expression and purification of Tp0319 recombinant protein of Treponema pallidum and its application in diagnosis of syphilis,” Journal of Clinical Laboratory Science, vol. 4, article 004, 2009. View at Google Scholar
  37. V. Sambri, A. Marangoni, C. Eyer et al., “Western immunoblotting with five Treponema pallidum recombinant antigens for serologic diagnosis of syphilis,” Clinical and Diagnostic Laboratory Immunology, vol. 8, no. 3, pp. 534–539, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. Xie, M. Xu, C. Wang et al., “Diagnostic value of recombinant Tp0821 protein in serodiagnosis for syphilis,” Letters in Applied Microbiology, vol. 62, no. 4, pp. 336–343, 2016. View at Publisher · View at Google Scholar · View at Scopus
  39. A. C. Seña, B. L. White, and P. F. Sparling, “Novel treponema pallidum serologic tests: a paradigm shift in syphilis screening for the 21st century,” Clinical Infectious Diseases, vol. 51, no. 6, pp. 700–708, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. L. Giacani, K. Hevner, and A. Centurion-Lara, “Gene organization and transcriptional analysis of the tprJ, tprI, tprG, and tprF loci in Treponema pallidum strains Nichols and Sea 81-4,” Journal of Bacteriology, vol. 187, no. 17, pp. 6084–6093, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. E. S. Sun, B. J. Molini, L. K. Barrett, A. Centurion-Lara, S. A. Lukehart, and W. C. Van Voorhis, “Subfamily I Treponema pallidum repeat protein family: sequence variation and immunity,” Microbes and Infection, vol. 6, no. 8, pp. 725–737, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Anand, M. LeDoyt, C. Karanian et al., “Bipartite topology of Treponema pallidum repeat proteins C/D and I: outer membrane insertion, trimerization, and porin function require a C-Terminal β-barrel domain,” Journal of Biological Chemistry, vol. 290, no. 19, pp. 12313–12331, 2015. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Centurion-Lara, R. E. LaFond, K. Hevner et al., “Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection,” Molecular Microbiology, vol. 52, no. 6, pp. 1579–1596, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. T. B. Reid, B. J. Molini, M. C. Fernandez, and S. A. Lukehart, “Antigenic variation of TprK facilitates development of secondary syphilis,” Infection and Immunity, vol. 82, no. 12, pp. 4959–4967, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. R. Heymans, M.-E. Kolader, J. J. Van Der Helm, R. A. Coutinho, and S. M. Bruisten, “TprK gene regions are not suitable for epidemiological syphilis typing,” European Journal of Clinical Microbiology and Infectious Diseases, vol. 28, no. 7, pp. 875–878, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. D. R. Blanco, J. N. Miller, and M. A. Lovett, “Surface antigens of the syphilis spirochete and their potential as virulence determinants,” Emerging Infectious Diseases, vol. 3, no. 1, pp. 11–20, 1997. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Xu, Y. Xie, C. Jiang et al., “A novel ELISA using a recombinant outer membrane protein, rTp0663, as the antigen for serological diagnosis of syphilis,” International Journal of Infectious Diseases, vol. 43, pp. 51–57, 2016. View at Publisher · View at Google Scholar · View at Scopus
  48. C. E. Cameron, S. A. Lukehart, C. Castro, B. Molini, C. Godornes, and W. C. Van Voorhis, “Opsonic potential, protective capacity, and sequence conservation of the Treponema pallidum subspecies pallidum Tp92,” Journal of Infectious Diseases, vol. 181, no. 4, pp. 1401–1413, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. D. C. Desrosiers, A. Anand, A. Luthra et al., “TP0326, a Treponema pallidumβ-barrel assembly machinery A (BamA) orthologue and rare outer membrane protein,” Molecular Microbiology, vol. 80, no. 6, pp. 1496–1515, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Luthra, A. Anand, K. L. Hawley et al., “A homology model reveals novel structural features and an immunodominant surface loop/opsonic target in the Treponema pallidum BamA ortholog TP_0326,” Journal of Bacteriology, vol. 197, no. 11, pp. 1906–1920, 2015. View at Publisher · View at Google Scholar · View at Scopus
  51. M. R. Kenedy, T. R. Lenhart, and D. R. Akins, “The role of Borrelia burgdorferi outer surface proteins,” FEMS Immunology and Medical Microbiology, vol. 66, no. 1, pp. 1–19, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. B. C. Smith, Y. Simpson, M. G. Morshed et al., “New proteins for a new perspective on syphilis diagnosis,” Journal of Clinical Microbiology, vol. 51, no. 1, pp. 105–111, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. K. R. O. Hazlett, D. L. Cox, M. Decaffmeyer et al., “TP0453, a concealed outer membrane protein of Treponema pallidum, enhances membrane permeability,” Journal of Bacteriology, vol. 187, no. 18, pp. 6499–6508, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Luthra, G. Zhu, D. C. Desrosiers et al., “The transition from closed to open conformation of Treponema pallidum outer membrane-associated lipoprotein TP0453 involves membrane sensing and integration by two amphipathic helices,” Journal of Biological Chemistry, vol. 286, no. 48, pp. 41656–41668, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. W. C. Van Voorhis, L. K. Barrett, S. A. Lukehart, B. Schmidt, M. Schriefer, and C. E. Cameron, “Serodiagnosis of syphilis: antibodies to recombinant Tp0453, Tp92, and Gpd proteins are sensitive and specific indicators of infection by Treponema pallidum,” Journal of Clinical Microbiology, vol. 41, no. 8, pp. 3668–3674, 2003. View at Publisher · View at Google Scholar · View at Scopus
  56. C. E. Cameron, E. L. Brown, J. M. Y. Kuroiwa, L. M. Schnapp, and N. L. Brouwer, “Treponema pallidum fibronectin-binding proteins,” Journal of Bacteriology, vol. 186, no. 20, pp. 7019–7022, 2004. View at Publisher · View at Google Scholar · View at Scopus
  57. C. V. Bamford, T. Francescutti, C. E. Cameron, H. F. Jenkinson, and D. Dymock, “Characterization of a novel family of fibronectin-binding proteins with M23 peptidase domains from Treponema denticola,” Molecular Oral Microbiology, vol. 25, no. 6, pp. 369–383, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. M. T. Dickerson, M. B. Abney, C. E. Cameron, M. Knecht, L. G. Bachas, and K. W. Anderson, “Fibronectin binding to the Treponema pallidum adhesin protein fragment rtp0483 on functionalized self-assembled monolayers,” Bioconjugate Chemistry, vol. 23, no. 2, pp. 184–195, 2012. View at Publisher · View at Google Scholar · View at Scopus
  59. P. R. Qing, Treponema pallidum adhesion proteins Tp0155, Tp0483 induce macrophage product inflammatory cytokine via activation of NF-κB [M.S. thesis], 2011.
  60. M. B. Brinkman, M. A. McGill, J. Pettersson et al., “A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin,” Infection and Immunity, vol. 76, no. 5, pp. 1848–1857, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. W. Ke, B. J. Molini, S. A. Lukehart, and L. Giacani, “Treponema pallidum subsp. pallidum TP0136 protein is heterogeneous among isolates and binds cellular and plasma fibronectin via its NH2-terminal end,” PLoS Neglected Tropical Diseases, vol. 9, no. 3, Article ID e0003662, 2015. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Yang, L. Shen, X.-X. Zhang, and Q. Sun, “Soluble expression, purification and characterization of recombinant Tp0136 selective fragment from Treponema pallidum,” Chinese Journal of Microbiology and Immunology, vol. 31, no. 2, pp. 119–123, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. C. E. Cameron, J. M. Y. Kuroiwa, M. Yamada, T. Francescutti, B. Chi, and H. K. Kuramitsu, “Heterologous expression of the Treponema pallidum laminin-binding adhesin Tp0751 in the culturable spirochete Treponema phagedenis,” Journal of Bacteriology, vol. 190, no. 7, pp. 2565–2571, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Houston, R. Hof, T. Francescutti, A. Hawkes, M. J. Boulanger, and C. E. Cameron, “Bifunctional role of the Treponema pallidum extracellular matrix binding adhesin Tp0751,” Infection and Immunity, vol. 79, no. 3, pp. 1386–1398, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Houston, S. Russell, R. Hof et al., “The multifunctional role of the pallilysin-associated Treponema pallidum protein, Tp0750, in promoting fibrinolysis and extracellular matrix component degradation,” Molecular Microbiology, vol. 91, no. 3, pp. 618–634, 2014. View at Publisher · View at Google Scholar · View at Scopus
  66. K. V. Lithgow, R. Hof, C. Wetherell, D. Phillips, S. Houston, and C. E. Cameron, “A defined syphilis vaccine candidate inhibits dissemination of Treponema pallidum subspecies pallidum,” Nature Communications, vol. 8, article 14273, 2017. View at Publisher · View at Google Scholar
  67. C. E. Stebeck, J. M. Shaffer, T. W. Arroll, S. A. Lukehart, and W. C. Van Voorhis, “Identification of the Treponema pallidum subsp. Pallidum glycerophosphodiester phosphodiesterase bomologue,” FEMS Microbiology Letters, vol. 154, no. 2, pp. 303–310, 1997. View at Publisher · View at Google Scholar · View at Scopus
  68. C. E. Cameron, C. Castro, S. A. Lukehart, and W. C. Van Voorhis, “Function and protective capacity of Treponema pallidum subsp. pallidum Glycerophosphodiester phosphodiesterase,” Infection and Immunity, vol. 66, no. 12, pp. 5763–5770, 1998. View at Google Scholar · View at Scopus
  69. J. D. Radolf, L. A. Borenstein, J. Y. Kim, T. E. Fehniger, and M. A. Lovett, “Role of disulfide bonds in the oligomeric structure and protease resistance of recombinant and native Treponema pallidum surface antigen 4D,” Journal of Bacteriology, vol. 169, no. 4, pp. 1365–1371, 1987. View at Publisher · View at Google Scholar · View at Scopus
  70. T. Pozzobon, N. Facchinello, F. Bossi et al., “Treponema pallidum (syphilis) antigen TpF1 induces angiogenesis through the activation of the IL-8 pathway,” Scientific Reports, vol. 6, Article ID 18785, 2016. View at Publisher · View at Google Scholar · View at Scopus
  71. C. Jiang, F. Zhao, J. Xiao et al., “Evaluation of the recombinant protein TpF1 of Treponema pallidum for serodiagnosis of syphilis,” Clinical and Vaccine Immunology, vol. 20, no. 10, pp. 1563–1568, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. C. Li, C. W. Wolgemuth, M. Marko, D. G. Morgan, and N. W. Charon, “Genetic analysis of spirochete flagellin proteins and their involvement in motility, filament assembly, and flagellar morphology,” Journal of Bacteriology, vol. 190, no. 16, pp. 5607–5615, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. S. J. Norris, “Polypeptides of Treponema pallidum: progress toward understanding their structural, functional, and immunologic roles. Treponema Pallidum Polypeptide Research Group,” Microbiological Reviews, vol. 57, no. 3, pp. 750–779, 1993. View at Google Scholar · View at Scopus
  74. C. Jiang, J. Xiao, Y. Xie et al., “Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis,” Diagnostic Microbiology and Infectious Disease, vol. 84, no. 2, pp. 105–111, 2016. View at Publisher · View at Google Scholar · View at Scopus