Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

Infection, Genetics and Evolution

Volumn 12, Issue 2, 2012, Pages 191-202

  Šmajs, David ^a   Norris, Steven J ^b   Weinstock, George M ^c  

^a MASARYK UNIVERSITY   (Czech Republic)

^b UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Molecular diagnostics; Molecular evolution; Treponema pallidum; Treponema pallidum ssp. endemicum; Treponema pallidum ssp. pertenue; Treponema paraluiscuniculi; Whole genome sequencing

Indexed keywords

BACTERIAL GENE; BACTERIAL GENOME; BACTERIAL STRAIN; BACTERIAL VIRULENCE; BACTERIUM ISOLATE; DNA FLANKING REGION; DNA METABOLISM; GENE ARP; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; GENE MAPPING; GENE MUTATION; GENE SEQUENCE; GENETIC DIFFERENCE; GENETIC VARIABILITY; GENOME ANALYSIS; GENOME SIZE; GENOTYPE; HUMAN; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOGENESIS; PATHOGENICITY ISLAND; PRIORITY JOURNAL; REVIEW; SYPHILIS; TPR GENE; TPRK GENE; TREPONEMA; TREPONEMA PALLIDUM; TREPONEMA PARALUISCUNICULI; TREPONEMATOSIS; YAWS;

ANIMALS; EVOLUTION, MOLECULAR; GENETIC VARIATION; HUMANS; MOLECULAR TYPING; RABBITS; SYPHILIS; TREPONEMA PALLIDUM; VIRULENCE FACTORS; YAWS;

ORYCTOLAGUS CUNICULUS; TREPONEMA; TREPONEMA PALLIDUM; TREPONEMA PARALUISCUNICULI;

EID: 84857659482     PISSN: 15671348     EISSN: 15677257     Source Type: Journal    
DOI: 10.1016/j.meegid.2011.12.001     Document Type: Review

References (135)

1. Achtman M. Evolution, population structure, and phylogeography of genetically monomorphic bacterial pathogens. Annu. Rev. Microbiol. 2008, 62:53-70.
2. Achtman M., Morelli G., Zhu P., Wirth T., Diehl I., Kusecek B., Vogler A.J., Wagner D.M., Allender C.J., Easterday W.R., Chenal-Francisque V., Worsham P., Thomson N.R., Parkhill J., Lindler L.E., Carniel E., Keim P. Microevolution and history of the plague bacillus, Yersinia pestis. Proc. Natl. Acad. Sci. USA 2004, 101:17837-17842.
3. Achtman M., Zurth K., Morelli G., Torrea G., Guiyoule A., Carniel E. Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proc. Natl. Acad. Sci. USA 1999, 96:14043-14048.
4. Antal G.M., Lukehart S.A., Meheus A.Z. The endemic treponematoses. Microbes Infect. 2002, 4:83-94.
5. Brinkman M.B., McGill M.A., Pettersson J., Rogers A., Matějková P., Šmajs D., Weinstock G.M., Norris S.J., Palzkill T. A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin. Infect. Immun. 2008, 76:1848-1857.
6. Brinkman M.B., McKevitt M., McLoughlin M., Perez C., Howell J., Weinstock G.M., Norris S.J., Palzkill T. Reactivity of antibodies from syphilis patients to a protein array representing the Treponema pallidum proteome. J. Clin. Microbiol. 2006, 44:888-891.
7. Cameron C.E., Castro C., Lukehart S.A., Van Voorhis W.C. Sequence conservation of glycerophosphodiester phosphodiesterase among Treponema pallidum strains. Infect. Immun. 1999, 67:3168-3170.
8. Cameron C.E., Lukehart S.A., Castro C., Molini B., Godornes C., Van Voorhis W.C. Opsonic potential, protective capacity, and sequence conservation of the Treponema pallidum subspecies pallidum Tp92. J. Infect. Dis. 2000, 181:1401-1413.
9. Castellani A. Further observations on parangi (Yaws). Br. Med. J. 1905, 1905:1330-1331.
10. Čejková, D., Zobaníková, M., Chen, L., PospíŠilová, P., Strouhal, M., Qin, X., Mikalová, L., Norris, S.J., Muzny, D.M., Gibbs, R.A., Fulton, L.L., Sodergren, E., Weinstock, G. M., Šmajs, D. in press. Whole genome sequences of three Treponema pallidum ssp. pertenue strains: yaws and syphilis treponemes differ in less than 0.2% of the genome sequence. PLoS Negl. Trop. Dis.
11. Centurion-Lara A., Castro C., Barrett L., Cameron C., Mostowfi M., Van Voorhis W.C., Lukehart S.A. Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response. J. Exp. Med. 1999, 189:647-656.
12. Centurion-Lara A., Castro C., Castillo R., Shaffer J.M., Van Voorhis W.C., Lukehart S.A. The flanking region sequences of the 15-kDa lipoprotein gene differentiate pathogenic treponemes. J. Infect. Dis. 1998, 177:1036-1040.
13. Centurion-Lara A., Godornes C., Castro C., Van Voorhis W.C., Lukehart S.A. The tprK gene is heterogenous among Treponema pallidum strains and has multiple alleles. Infect. Immun. 2000, 68:824-831.
14. Centurion-Lara A., LaFond R.E., Hevner K., Godornes C., Molini B.J., Van Voorhis W.C., Lukehart S.A. Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection. Mol. Microbiol. 2004, 52:1579-1596.
15. Centurion-Lara A., Molini B.J., Godornes C., Sun E., Hevner K., Van Voorhis W.C., Lukehart S.A. Molecular differentiation of Treponema pallidum subspecies. J. Clin. Microbiol. 2006, 44:3377-3380.
16. Centurion-Lara A., Sun E.S., Barrett L.K., Castro C., Lukehart S.A., Van Voorhis W.C. Multiple alleles of Treponema pallidum repeat gene D in Treponema pallidum isolates. J. Bacteriol. 2000, 182:2332-2335.
17. Chacko C.W. Accidental human infection in the laboratory with Nichols rabbit-adapted virulent strain of Treponema pallidum. Bull. World Health Organ. 1966, 35:809-810.
18. Chen C.Y., Chi K.H., Pillay A., Nachamkin E., Ballard R. Detection of the 23S rRNA point mutations (A2058G and A2059G) associated with azithromycin resistance in Treponema pallidum using a TaqMan-based real-time Triplex-PCR assay. Sex. Transm. Dis. 2011, 87(Suppl.):A298.
19. Citti C., Kim M.F., Wise K.S. Elongated versions of Vlp surface lipoproteins protect Mycoplasma hyorhinis escape variants from growth-inhibiting host antibodies. Infect. Immun. 1997, 65:1773-1785.
20. Cole M.J., Chisholm S.A., Palmer H.M., Wallace L.A., Ison C.A. Molecular epidemiology of syphilis in Scotland. Sex. Transm. Infect. 2009, 85:447-451.
21. Cox D.L., Luthra A., Dunham-Ems S., Desrosiers D.C., Salazar J.C., Caimano M.J., Radolf J.D. Surface immunolabeling and consensus computational framework to identify candidate rare outer membrane proteins of Treponema pallidum. Infect. Immun. 2010, 78:5178-5194.
22. Cullen T.W., Trent M.S. A link between the assembly of flagella and lipooligosaccharide of the Gram-negative bacterium Campylobacter jejuni. Proc. Natl Acad. Sci. USA 2010, 107:5160-5165.
23. de Melo F.L., de Mello J.C., Fraga A.M., Nunes K., Eggers S. Syphilis at the crossroad of phylogenetics and paleopathology. PLoS Negl. Trop. Dis. 2010, 4:e575.
24. Denoeud F., Vergnaud G. Identification of polymorphic tandem repeats by direct comparison of genome sequence from different bacterial strains: a web-based resource. BMC Bioinf. 2004, 5:4.
25. DiGiacomo R.F., Lukehart S.A., Talburt C.D., Baker-Zander S.A., Condon J., Brown C.W. Clinical course and treatment of venereal spirochaetosis in New Zealand white rabbits. Br. J. Venereol. Dis. 1984, 60:214-218.
26. DiGiacomo R.F., Lukehart S.A., Talburt C.D., Baker-Zander S.A., Giddens W.E., Condon J., Brown C.W. Chronicity of infection with Treponema paraluis-cuniculi in New Zealand white rabbits. Genitourin. Med. 1985, 61:156-164.
27. DiGiacomo R.F., Talburt C.D., Lukehart S.A., Baker-Zander S.A., Condon J. Treponema paraluis-cuniculi infection in a commercial rabbitry: epidemiology and serodiagnosis. Lab. Anim. Sci. 1983, 33:562-566.
28. Dos Vultos T., Mestre O., Rauzier J., Golec M., Rastogi N., Rasolofo V., Tonjum T., Sola C., Matic I., Gicquel B. Evolution and diversity of clonal bacteria: the paradigm of Mycobacterium tuberculosis. PLoS ONE 2008, 2:e1538.
29. Fieldsteel A.H., Cox D.L., Moeckli R.A. Cultivation of virulent Treponema pallidum in tissue culture. Infect. Immun. 1981, 32:908-915.
30. Fitzgerald J.J., Johnson R.C., Smith M. Accidental laboratory infection with Treponema pallidum, Nichols strain. J. Am. Venereol. Dis. Assoc. 1976, 3:76-78.
31. Flasarová, M., PospíŠilová, P., Mikalová, L., ValiŠová, Z., Dastychová, E., Strnadel, R.V., Kuklová, I., Woznicová, V., Zákoucká, H., Šmajs, D. in press. Sequencing-based molecular typing of Treponema pallidum strains in the Czech Republic: all identified genotypes are related to the sequence of the SS14 strain. Acta Derm. Venereol.
32. Flasarová M., Šmajs D., Matějková P., Woznicová V., Heroldová-Dvořáková M., Votava M. Molecular detection and subtyping of Treponema pallidum subsp. Pallidum in clinical specimens. Epidemiol. Mikrobiol. Imunol. 2006, 55:105-111.
33. Florindo C., Reigado V., Gomes J.P., Azevedo J., Santo I., Borrego M.J. Molecular typing of Treponema pallidum clinical strains from Lisbon. Portugal. J. Clin. Microbiol. 2008, 46:3802-3803.
34. Fraser C.M., Norris S.J., Weinstock G.M., White O., Sutton G.G., Dodson R., Gwinn M., Hickey E.K., Clayton R., Ketchum K.A., Sodergren E., Hardham J.M., McLeod M.P., Salzberg S., Peterson J., Khalak H., Richardson D., Howell J.K., Chidambaram M., Utterback T., MacDonald L., Artiach P., Bowman C., Cotton M.D., Fujii C., Garland S., Hatch B., Horst K., Roberts K., Sandusky M., Weidman J., Smith H.O., Venter J.C. Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 1998, 281:375-388.
35. Fribourg-Blanc A., Mollaret H.H. Natural treponematotis of the African primate. Primates Med. 1969, 3:113-121.
36. Gastinel P., Vaisman A., Hamelin A., Dunoyer F. Study of a recently isolated strain of Treponema pertenue. Ann. Dermatol. Syphiligr. Paris 1963, 90:155-161.
37. Giacani L., Sun E.S., Hevner K., Molini B.J., Van Voorhis W.C., Lukehart S.A., Centurion-Lara A. Tpr homologs in Treponema paraluiscuniculi Cuniculi A strain. Infect. Immun. 2004, 72:6561-6576.
38. Giacani L., Lukehart S., Centurion-Lara A. Length of guanosine homopolymeric repeats modulates promoter activity of subfamily II tpr genes of Treponema pallidum ssp. Pallidum. FEMS Immunol. Med. Microbiol. 2007, 51:289-301.
39. Giacani L., Godornes C., Puray-Chavez M., Guerra-Giraldez C., Tompa M., Lukehart S.A., Centurion-Lara A. TP0262 is a modulator of promoter activity of tpr Subfamily II genes of Treponema pallidum ssp. Pallidum. Mol. Microbiol. 2009, 72:1087-1099.
40. Giacani L., Jeffrey B.M., Molini B.J., Le H.T., Lukehart S.A., Centurion-Lara A., Rockey D.D. Complete genome sequence and annotation of the Treponema pallidum subsp pallidum Chicago strain. J. Bacteriol. 2010, 192:2645-2646.
41. Giacani L., Molini B.J., Kim E.Y., Godornes B.C., Leader B.T., Tantalo L.C., Centurion-Lara A., Lukehart S.A. Antigenic variation in Treponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis. J. Immunol. 2010, 184:3822-3829.
42. Godoy D., Randle G., Simpson A.J., Aanensen D.M., Pitt T.L., Kinoshita R., Spratt B.G. Multilocus sequence typing and evolutionary relationships among the causative agents of melioidosis and glanders, Burkholderia pseudomallei and Burkholderia mallei. J. Clin. Microbiol. 2003, 41:2068-2079.
43. Graves S., Downes J. Experimental infection of man with rabbit-virulent Treponema paraluis-cuniculi. Br. J. Venereol. Dis. 1981, 57:7-10.
44. Gray R.R., Mulligan C.J., Molini B.J., Sun E.S., Giacani L., Godornes C., Kitchen A., Lukehart S.A., Centurion-Lara A. Molecular evolution of the tprC, D, I, K, G, and J genes in the pathogenic genus Treponema. Mol. Biol. Evol. 2006, 23:2220-2233.
45. Harper K.N., Liu H., Ocampo P.S., Steiner B.M., Martin A., Levert K., Wang D., Sutton M., Armelagos G.J. The sequence of the acidic repeat protein (arp) gene diferentiates venereal from nonvenereal Treponema pallidum subspecies, and the gene has evolved under strong positive selection in the subspecies that causes syphilis. FEMS Immunol. Med. Microbiol. 2008, 53:322-332.
46. Harper K.N., Ocampo P.S., Steiner B.M., George R.W., Silverman M.S., Bolotin S., Pillay A., Saunders N.J., Armelagos G.J. On the origin of the treponematoses: a phylogenetic approach. PloS Negl. Trop. Dis. 2008, 2:e148.
47. Hazlett K.R., Sellati T.J., Nguyen T.T., Cox D.L., Clawson M.L., Caimano M.J., Radolf J.D. The TprK protein of Treponema pallidum is periplasmic and is not a target of opsonic antibody or protective immunity. J. Exp. Med. 2001, 193:1015-1026.
48. Heymans R., Kolader M.-E., van der Helm J.J., Coutinho R.A., Bruisten S.M. TprK gene regions are not suitable for epidemiological syphilis typing. Eur. J. Clin. Microbiol. Infect. Dis. 2009, 28:875-878.
49. Hood D.W., Deadman M.E., Jennings M.P., Bisercic M., Fleischmann R.D., Venter J.C., Moxon E.R. DNA repeats identify novel virulence genes in Haemophilus influenzae. Proc. Natl. Acad. Sci. USA 1996, 93:11121-11125.
50. Jacobsthal E. Untersuchungen über eine syphilisähnliche Spontanerkrankungen des Kaninchens (Paralues cuniculi). Derm. Wschr. 1920, 71:569-571.
51. Katz K.A., Pillay A., Ahrens K., Kohn R.P., Hermanstyne K., Bernstein K.T., Ballard R.C., Klausner J.D. Molecular epidemiology of syphilis - San Francisco, 2004-2007. Sex. Transm. Dis. 2010, 37:660-663.
52. Kidgell C., Reichard U., Wain J., Linz B., Torpdahl M., Dougan G., Achtman M. Salmonella typhi, the causative agent of typhoid fever, is approximately 50,000 years old. Infect. Genet. Evol. 2002, 2:39-45.
53. Knauf, S., Batamuzi, E.K., Mlengeya, T., Kilewo, M., Lejora, I.A., Nordhoff, M., Ehlers, B., Harper, K.N., Fyumagwa, R., Hoare, R., Failing, K., Wehrend, A., Kaup, F.J., Leendertz, F.H., Mätz-Rensing, K., 2011. Treponema Infection Associated With Genital Ulceration in Wild Baboons. Vet. Pathol. [Epub ahead of print].
54. Krieg N.R., Staley J.T., Brown D.R., Hedlund B.P., Paster B.J., Ward N.L., Ludwig W., Whitman W.B. Bergey's Manual of Systematic Bacteriology 2010, Springer, New York, pp. 501-531. second ed.
55. LaFond R.E., Centurion-Lara A., Godornes C., Rompalo A.M., Van Voorhis W.C., Lukehart S.A. Sequence diversity of Treponema pallidum subsp. Pallidum tprK in human syphilis lesions and rabbit-propagated isolates. J. Bacteriol. 2003, 185:6262-6268.
56. LaFond R.E., Centurion-Lara A., Godornes C., Van Voorhis W.C., Lukehart S.A. TprK sequence diversity accumulates during infection of rabbits with Treponema pallidum subsp. Pallidum Nichols strain. Infect. Immun. 2006, 74:1896-1906.
57. Leader B.T., Hevner K., Molini B.J., Barrett L.K., Van Voorhis W.C., Lukehart S.A. Antibody responses elicited against the Treponema pallidum repeat proteins differ during infection with different isolates of Treponema pallidum subsp. Pallidum. Infect. Immun. 2003, 71:6054-6057.
58. Levaditi C., Marie A., Nicolau S. Virulence pour l'homme du spirochète de la spirillose spontanée du lapin. C.R. Acad. Sci. 1921, 172:1542-1543.
59. Liska S.L., Perine P.L., Hunter E.F., Crawford J.A., Feelez J.C. Isolation and transportation of Treponema pertenue in golden hamsters. Curr. Microbiol. 1982, 7:41-43.
60. Liu H., Rodes B., George R., Steiner B. Molecular characterization and analysis of a gene encoding the acidic repeat protein (Arp) of Treponema pallidum. J. Med. Microbiol. 2007, 56:715-721.
61. Livingstone F.B. On the origin of syphilis: an alternative hypothesis. Curr. Anthropol. 1991, 32:587-590.
62. Lukehart S.A., Godornes C., Molini B.J., Sonnett P., Hopkins S., Mulcahy F., Engelman J., Mitchell S.J., Rompalo A.M., Marra C.M., Klausner J.D. Macrolide resistance in Treponema pallidum in the United States and Ireland. N. Engl. J. Med. 2004, 351:154-158.
63. MacDougall J., Saint Girons I. Physical map of the Treponema denticola circular chromosome. J. Bacteriol. 1995, 177:1805-1811.
64. Magnuson H.J., Thomas E.W., Olansky S., Kaplan B.I., de Mello L., Cutler J.C. Inoculation syphilis in human volunteers. Medicine (Baltimore) 1956, 35:33-82.
65. Marra C.M., Colina A.P., Godornes C., Tantalo L.C., Puray M., Centurion-Lara A., Lukehart S.A. Antibiotic selection may contribute to increases in macrolide-resistant Treponema pallidum. J. Infect. Dis. 2006, 194:1771-1773.
66. Marra C.M., Sahi S.K., Tantalo L.C., Godornes C., Reid T., Behets F., Rompalo A., Klausner J.D., Yin Y.P., Mulcahy F., Golden M.R., Centurion-Lara A., Lukehart S.A. Enhanced molecular typing of Treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J. Infect. Dis. 2010, 202:1380-1388.
67. Martin I.E., Gu W., Yang Y., Tsang R.S.W. Macrolide resistance and molecular types of Treponema pallidum causing primary syphilis in Shanghai. Chin. Clin. Infect. Dis. 2009, 49:515-521.
68. Martin I.E., Tsang R.S., Sutherland K., Anderson B., Read R., Roy C., Yanow S., Fonseca K., White W., Kandola K., Kouadjo E., Singh A.E. Molecular typing of Treponema pallidum strains in western Canada: predominance of 14d subtypes. Sex. Transm. Dis. 2010, 37:544-548.
69. Martin I.E., Tsang R.S.W., Sutherland K., Tilley P., Read R., Anderson B., Roy C., Singh A.E. Molecular characterization of syphilis in pacients in Canada: azitromycin resistance and detection of Treponema pallidum DNA in whole-blood samples versus ulcerative swabs. J. Clin. Microbiol. 2009, 47:1668-1673.
70. Matějková P., Flasarová M., Zákoucká H., Bořek M., Křemenová S., Arenberger P., Woznicová V., Weinstock G.M., Šmajs D. Macrolide treatment failure in a case of secondary syphilis: a novel A2059G mutation in the 23S rRNA gene of Treponema pallidum subsp. Pallidum. J. Med. Microbiol. 2009, 58:832-836.
71. Matějková P., Strouhal M., Šmajs D., Norris S.J., Palzkill T., Petrosino J.F., Sodergren E., Norton J.E., Singh J., Richmond T.A., Molla M.N., Albert T.J., Weinstock G.M. Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays. BMC Microbiol. 2008, 8:76.
72. Mays S., Crane-Kramer G., Bayliss A. Two probable cases of treponemal disease of Medieval date from England. Am. J. Phys. Anthropol. 2003, 120:133-143.
73. McGill M.A., Edmondson D.G., Carroll J.A., Cook R.G., Orkiszewski R.S., Norris S.J. Characterization and serologic analysis of the Treponema pallidum proteome. Infect. Immun. 2010, 78:2631-2643.
74. McKevitt M., Brinkman M.B., McLoughlin M., Perez C., Howell J.K., Weinstock G.M., Norris S.J., Palzkill T. Genome scale identification of Treponema pallidum antigens. Infect. Immun. 2005, 73:4445-4450.
75. McKevitt M., Patel K., Šmajs D., Marsh M., McLoughlin M., Norris S.J., Weinstock G.M., Palzkill T. Systematic cloning of Treponema pallidum open reading frames for protein expression and antigen discovery. Genome Res. 2003, 13:1665-1674.
76. Meyer C., Jung C., Kohl T., Poenicke A., Poppe A., Alt K.W. Syphilis 2001 - A palaeopathological reappraisal. Homo 2002, 53:39-58.
77. Miao R.M., Fieldsteel A.H. Genetics of Treponema: relationship between Treponema pallidum and five cultivable treponemes. J. Bacteriol. 1978, 133:101-107.
78. Miao R.M., Fieldsteel A.H. Genetic relationship between Treponema pallidum and Treponema pertenue, two noncultivable human pathogens. J. Bacteriol. 1980, 141:427-429.
79. Mikalová L., Strouhal M., čejková D., Zobaníková M., PospíŠilová P., Norris S.J., Sodergren E., Weinstock G.M., Šmajs D. Genome analysis of Treponema pallidum subsp. Pallidum and subsp. pertenue strains: most of the genetic differences are localized in six regions. PLoS One 2010, 5:e15713.
80. Miller J.N. Immunity in experimental syphilis. VI. Successful vaccination of rabbits with Treponema pallidum, Nichols strain, attenuated by -irradiation. J. Immunol. 1973, 110:1206-1215.
81. Mitchell S.J., Engelman J., Kent C.K., Lukehart S.A., Godornes C., Klausner J.D. Azithromycin-resistant syphilis infection: San Francisco, California, 2000-2004. Clin. Infect. Dis. 2006, 42:337-345.
82. Molepo J., Pillay A., Weber B., Morse S.A., Hoosen A.A. Molecular typing of Treponema pallidum strains from patients with neurosyphilis in Pretoria, South Africa. Sex. Transm. Infect. 2007, 83:189-192.
83. Monot M., Honoré N., Garnier T., Araoz R., Coppée J.-Y., Lacroix C., Sow S., Spencer J.S., Truman R.W., Williams D.L., Gelber R., Virmond M., Flageul B., Cho S.-N., Ji B., Paniz-Mondolfi A., Convit J., Young S., Fine P.E., Rasolofo V., Brennan P.J., Cole S.T. On the origin of leprosy. Science 2005, 308:1040-1042.
84. Morgan C.A., Lukehart S.A., Van Voorhis W.C. Immunization with the N-terminal portion of Treponema pallidum repeat protein K attenuates syphilitic lesion development in the rabbit model. Infect. Immun. 2002, 70:6811-6816.
85. Morgan C.A., Lukehart S.A., Van Voorhis W.C. Protection against syphilis correlates with specificity of antibodies to the variable regions of Treponema pallidum repeat protein K. Infect. Immun. 2003, 71:5605-5612.
86. Morgan C.A., Molini B.J., Lukehart S.A., Van Voorhis W.C. Segregation of B and T cell epitopes of Treponema pallidum repeat protein K to variable and conserved regions during experimental syphilis infection. J. Immunol. 2002, 169:952-957.
87. Mulligan C.J., Norris S.J., Lukehart S.A. Molecular studies in Treponema pallidum evolution: toward clarity?. PloS Negl. Trop. Dis. 2008, 2:e184.
88. Naranjo P. On the American Indian origin of syphilis: fallacies and errors. Allergy Proc. 1994, 15:89-99.
89. Nichols H.J., Hough W.H. Demonstration of Spirochaeta pallida in the cerebrospinal fluid. JAMA, J. Am. Med. Assoc. 1913, 60:108-110.
90. Noordhoek G.T., Hermans P.W., Paul A.N., Schouls L.M., van der Sluis J.J., van Embden J.D. Treponema pallidum subspecies pallidum (Nichols) and Treponema pallidum subspecies pertenue (CDC 2575) differ in at least one nucleotide: comparison of two homologous antigens. Microb. Pathog. 1989, 6:29-42.
91. Noordhoek G.T., Wieles B., van der Sluis J.J., van Embden J.D. Polymerase chain reaction and synthetic DNA probes: a means of distinguishing the causative agents of syphilis and yaws?. Infect. Immun. 1990, 58:2011-2013.
92. Palmer G.H., Bankhead T., Lukehart S.A. 'Nothing is permanent but change' - antigenic variation in persistent bacterial pathogens. Cell. Microbiol. 2009, 11:1697-1705.
93. Pearson T., Busch J.D., Ravel J., Read T.D., Rhoton S.D., U'Ren J.M., Simonson T.S., Kachur S.M., Leadem R.R., Cardon M.L., Van Ert M.N., Huynh L.Y., Fraser C.M., Keim P. Phylogenetic discovery bias in Bacillus anthracis using single-nucleotide polymorphisms from whole-genome sequencing. Proc. Natl Acad. Sci. USA 2004, 101:13536-13541.
94. Pillay A., Liu H., Chen C.Y., Holloway B., Sturm A.W., Steiner B., Morse S.A. Molecular subtyping of Treponema pallidum subspecies pallidum. Sex. Transm. Dis. 1998, 25:408-414.
95. Pillay A., Liu H., Ebrahim S., Chen C.Y., Lai W., Fehler G., Ballard R.C., Steiner B., Sturm A.W., Morse S.A. Molecular typing of Treponema pallidum in South Africa: cross-sectional studies. J. Clin. Microbiol. 2002, 40:256-258.
96. Pope V., Fox K., Liu H., Marfin A.A., Leone P., Seña A.C., Chapin J., Fears M.B., Markowitz L. Molecular subtyping of Treponema pallidum from North and South Carolina. J. Clin. Microbiol. 2005, 43:3743-3746.
97. Powell M.L., Cook D.C. The myth of syphilis: The natural history of treponematosis in North America 2005, University Press of Florida, Gainsville, p. 544.
98. Rattei T., Ott S., Gutacker M., Rupp J., Maass M., Schreiber S., Solbach W., Wirth T., Gieffers J. Genetic diversity of the obligate intracellular bacterium Chlamydophila pneumoniae by genome-wide analysis of single nucleotide polymorphism: evidence for highly clonal population structure. BMC Genomics 2007, 8:355.
99. Román G.C., Román L. Occurence of congenital, cardiovascular, visceral, neurologic, and neuro-ophthalmologic complications in late yaws: a theme for future research. Rev. Infect. Dis. 1986, 8:760-777.
100. Rompalo A.M. Can syphilis be eradicated from the world?. Curr. Opin. Infect. Dis. 2001, 14:41-44.
101. Rothschild B.M. History of syphilis. Clin. Infect. Dis. 2005, 40:1454-1463.
102. Rothschild C., Rothschild B.M. Occurrence and transitions among the treponematoses in North America. Chungara, Revista de Antropologia Chilena 2000, 32:147-155.
103. Roumagnac P., Weill F.-X., Dolecek C., Baker S., Brisse S., Chinh N.T., Le T.A.H., Acosta C.J., Farrar J., Dougan G., Achtman M. Evolutionary history of Salmonella typhi. Science 2006, 314:1301-1304.
104. Saunders N.J., Jeffries A.C., Peden J.F., Hood D.W., Tettelin H., Rappuoli R., Moxon E.R. Repeat-associated phase variable genes in the complete genome sequence of Neisseria meningitidis strain MC58. Mol. Microbiol. 2000, 37:207-215.
105. Schell R.F., Azadegan A.A., Nitskansky S.G., LeFrock J.L. Acquired resistance of hamsters to challenge with homologous and heterologous virulent treponemes. Infect. Immun. 1982, 37:617-621.
106. Schmidt H., Hensel M. Pathogenicity islands in bacterial pathogenesis. Clin. Microbiol. Rev. 2004, 17:14-56.
107. Seshadri R., Myers G.S., Tettelin H., Eisen J.A., Heidelberg J.F., Dodson R.J., Davidsen T.M., DeBoy R.T., Fouts D.E., Haft D.H., Selengut J., Ren Q., Brinkac L.M., Madupu R., Kolonay J., Durkin S.A., Daugherty S.C., Shetty J., Shvartsbeyn A., Gebregeorgis E., Geer K., Tsegaye G., Malek J., Ayodeji B., Shatsman S., McLeod M.P., Šmajs D., Howell J.K., Pal S., Amin A., Vashisth P., McNeill T.Z., Xiang Q., Sodergren E., Baca E., Weinstock G.M., Norris S.J., Fraser C.M., Paulsen I.T. Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes. Proc. Natl Acad. Sci. USA 2004, 101:5646-5651.
108. Šmajs D., McKevitt M., Howell J.K., Norris S.J., Cai W.W., Palzkill T., Weinstock G.M. Transcriptome of Treponema pallidum: gene expression profile during experimental rabbit infection. J. Bacteriol. 2005, 187:1866-1874.
109. Šmajs D., McKevitt M., Wang L., Howell J.K., Norris S.J., Palzkill T., Weinstock G.M. BAC library of T. Pallidum DNA in E. coli. Genome Res. 2002, 12:515-522.
110. Šmajs D., Zobaníková M., Strouhal M., čejková D., Dugan-Rocha S., PospíŠilová P., Norris S.J., Albert T., Qin X., Hallsworth-Pepin K., Buhay C., Muzny D.M., Chen L., Gibbs R.A., Weinstock G.M. Complete genome sequence of Treponema paraluiscuniculi, strain Cuniculi A: the loss of infectivity to humans is associated with genome decay. PLoS ONE 2011, 6:e20415.
111. AL. Bergey's Manual of Systematic Bacteriology, vol. 1 1984, 49-57. The Williams & Wilkins Co., Baltimore. N.R. Krieg, J.G. Holt (Eds.).
112. Smith J.L. Neuro-ophthalmological study of late yaws. I. An introduction to yaws. Br. J. Venereol. Dis. 1971, 47:223-225.
113. Smith J.L., David N.J., Indgin S., Israel C.W., Levine B.M., Justice J., McCrary J.A., Medina R., Paez P., Santana E., Sarkar M., Schatz N.J., Spitzer M.L., Spitzer W.O., Walter E.K. Neuro-ophthalmological study of late yaws and pinta. II. The Caracas project. Br. J. Venereol. Dis. 1971, 47:226-251.
114. Smith J.L., Pesetsky B.R. The current status of Treponema cuniculi: review of the literature. Br. J. Venereol. Dis. 1967, 43:117-127.
115. Stamm L.V., Bergen H.L. A point mutation associated with bacterial macrolide resistance is present in both 23S rRNA genes of an erythromycin-resistant Treponema pallidum clinical isolate. Antimicrob. Agents Chemother. 2000, 44:806-807.
116. Stamm L.V., Gherardini F.C., Parrish E.A., Moomaw C.R. Heat shock response of spirochetes. Infect. Immun. 1991, 59:1572-1575.
117. Stamm L.V., Greene S.R., Bergen H.L., Hardham J.M., Barnes N.Y. Identification and sequence analysis of Treponema pallidum tprJ, a member of a polymorphic multigene family. FEMS Microbiol. Lett. 1998, 169:155-163.
118. Stamm L.V., Kerner T.C., Bankaitis V.A., Bassford P.J. Identification and preliminary characterization of Treponema pallidum protein antigens expressed in Escherichia coli. Infect. Immun. 1983, 41:709-721.
119. Strouhal M., Šmajs D., Matějková P., Sodergren E., Amin A.G., Howell J.K., Norris S.J., Weinstock G.M. Genome differences between Treponema pallidum subsp. Pallidum strain Nichols and T. paraluiscuniculi strain Cuniculi A. Infect. Immun. 2007, 75:5859-5866.
120. Sutton M.Y., Liu H., Steiner B., Pillay A., Mickey T., Finelli L., Morse S., Markowitz L.E., St.Louis M.E. Molecular subtyping of Treponema pallidum in an Arizona Country with increasing syphilis morbidity: use of specimens from ulcers and blood. J. Infect. Dis. 2001, 183:1601-1606.
121. Tantalo L.C., Lukehart S.A., Marra C.M. Treponema pallidum strain-specific differences in neuroinvasion and clinical phenotype in a rabbit model. J. Infect. Dis. 2005, 191:75-80.
122. Tipple C., McClure M.O., Taylor G.P. High prevalence of macrolide resistant Treponema pallidum strains in a London centre. Sex. Transm. Infect. 2011, 87:486-488.
123. Titz B., Rajagopala S.V., Goll J., Häuser R., McKevitt M.T., Palzkill T., Uetz P. The binary protein interactome of Treponema pallidum - The syphilis spirochete. PLoS ONE 2008, 3:e2292.
124. Turner T.B., Hollander D.H. Biology of the treponematoses based on studies carried out at the International Treponematosis Laboratory Center of the Johns Hopkins University under the auspices of the World Health Organization. Monogr. Ser. World Health Organ. 1957, 35:3-266.
125. Van Damme K., Behets F., Ravelomanana N., Godornes C., Khan M., Randrianasolo B., Rabenja N.L., Lukehart S., Cohen M., Hook E. Evaluation of azithromycin resistance in Treponema pallidum specimens from Madagascar. Sex. Transm. Dis. 2009, 36:775-776.
126. Van Ert M.N., Easterday W.R., Huynh L.Y., Okinaka R.T., Hugh-Jones M.E., Ravel J., Zanecki S.R., Pearson T., Simonson T.S., U'Ren J.M., Kachur S.M., Leadem-Dougherty R.R., Rhoton S.D., Zinser G., Farlow J., Coker P.R., Smith K.L., Wang B., Kenefic L.J., Fraser-Liggett C.M., Wagner D.M., Keim P. Global genetic population structure of Bacillus anthracis. PLoS ONE 2007, 2:e461.
127. Visser M.B., Ellen R.P. New insights into the emerging role of oral spirochaetes in periodontal disease. Clin. Microbiol. Infect. 2011, 17:502-512.
128. Walker E.M., Howell J.K., You Y., Hoffmaster A.R., Heath J.D., Weinstock G.M., Norris S.J. Physical map of the genome of Treponema pallidum subsp. Pallidum (Nichols). J. Bacteriol. 1995, 177:1797-1804.
129. Weinstock G.M., Hardham J.M., McLeod M.P., Sodergren E.J., Norris S.J. The genome of Treponema pallidum: new light on the agent of syphilis. FEMS Microbiol. Rev. 1998, 22:323-332.
130. Weinstock G.M., Norris S.J., Sodergren E., Šmajs D. Identification of virulence genes in silico: infectious disease genomics. Virulence Mechanisms of Bacterial Pathogens 2000, 251-261. American Society for Microbiology Press, Washington, DC. third ed. K.A. Brogden (Ed.).
131. Weinstock G.M., Šmajs D., Hardham J., Norris S.J. From microbial genome sequence to applications. Res. Microbiol. 2000, 151:151-158.
132. Wendel G.D., Sanchez P.J., Peters M.T., Harstad T.W., Potter L.L., Norgard M.V. Identification of Treponema pallidum in amniotic fluid and fetal blood from pregnancies comlicated by congenital syphilis. Obstet. Gynecol. 1991, 78:890-895.
133. World Health Organization The world health report 1998 - Life in the 21st century: a vision for all 1998, World Health Organization, Geneva, pp. 132.
134. Woznicová V., Matějková P., Flasarová M., Zákoucká H., ValiŠová Z., Šmajs D., Dastychová E. Clarithromycin treatment failure due to macrolide resistance in Treponema pallidum in a patient with primary syphilis. Acta Derm. Venereol. 2010, 90:206-207.
135. Woznicová V., Šmajs D., Wechsler D., Matějková P., Flasarová M. Detection of Treponema pallidum subsp. Pallidum from skin lesions, serum, and cerebrospinal fluid in an infant with congenital syphilis after clindamycin treatment of the mother during pregnancy. J. Clin. Microbiol. 2007, 45:659-661.