BACKGROUND: Treponema pallidum ssp. pallidum (TPA), the causative agent of syphilis, and Treponema pallidum ssp. pertenue (TPE), the causative agent of yaws, are closely related spirochetes causing diseases with distinct clinical manifestations. The TPA Mexico A strain was isolated in 1953 from male, with primary syphilis, living in Mexico. Attempts to cultivate TPA Mexico A strain under in vitro conditions have revealed lower growth potential compared to other tested TPA strains. METHODOLOGY/PRINCIPAL FINDINGS: The complete genome sequence of the TPA Mexico A strain was determined using the Illumina sequencing technique. The genome sequence assembly was verified using the whole genome fingerprinting technique and the final sequence was annotated. The genome size of the Mexico A strain was determined to be 1,140,038 bp with 1,035 predicted ORFs. The Mexico A genome sequence was compared to the whole genome sequences of three TPA (Nichols, SS14 and Chicago) and three TPE (CDC-2, Samoa D and Gauthier) strains. No large rearrangements in the Mexico A genome were found and the identified nucleotide changes occurred most frequently in genes encoding putative virulence factors. Nevertheless, the genome of the Mexico A strain, revealed two genes (TPAMA_0326 (tp92) and TPAMA_0488 (mcp2-1)) which combine TPA- and TPE- specific nucleotide sequences. Both genes were found to be under positive selection within TPA strains and also between TPA and TPE strains. CONCLUSIONS/SIGNIFICANCE: The observed mosaic character of the TPAMA_0326 and TPAMA_0488 loci is likely a result of inter-strain recombination between TPA and TPE strains during simultaneous infection of a single host suggesting horizontal gene transfer between treponemal subspecies.

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Zobrazit více v PubMed

Schaudin FR, Hoffmann E (1905) Vorläufiger Bericht über das Vorkommen von Spirochaeten in syphilitischen Krankheitsprodukten und bei Papillomen. Arb K Gesund 22: 527–534. PubMed

Castellani A (1905) Further Observations on Parangi (Yaws). Br Med J 2: 1330–1331. PubMed PMC

World Health Organization (1998) The world health report - Life in the 21st Century: A vision for all.

Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, et al. (1998) Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281: 375–388. PubMed

Matejkova P, Strouhal M, Smajs D, Norris SJ, Palzkill T, et al. (2008) Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays. BMC Microbiol 8: 76. PubMed PMC

Giacani L, Jeffrey BM, Molini BJ, Le HT, Lukehart SA, et al. (2010) Complete genome sequence and annotation of the Treponema pallidum subsp. pallidum Chicago strain. J Bacteriol 192: 2645–2646. PubMed PMC

Cejkova D, Zobanikova M, Chen L, Pospisilova P, Strouhal M, et al. (2012) 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 6: e1471. PubMed PMC

Smajs D, Zobanikova M, Strouhal M, Cejkova D, Dugan-Rocha S, et al. (2011) Complete genome sequence of Treponema paraluiscuniculi, strain Cuniculi A: the loss of infectivity to humans is associated with genome decay. PLoS One 6: e20415. PubMed PMC

Mikalova L, Strouhal M, Cejkova D, Zobanikova M, Pospisilova P, et al. (2010) Genome analysis of Treponema pallidum subsp. pallidum and subsp. pertenue strains: most of the genetic differences are localized in six regions. PLoS One 5: e15713. PubMed PMC

Smajs D, Norris SJ, Weinstock GM (2012) Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws. Infect Genet Evol PubMed PMC

Centurion-Lara A, Sun ES, Barrett LK, Castro C, Lukehart SA, et al. (2000) Multiple alleles of Treponema pallidum repeat gene D in Treponema pallidum isolates. J Bacteriol 182: 2332–2335. PubMed PMC

Gray RR, Mulligan CJ, Molini BJ, Sun ES, Giacani L, et al. (2006) Molecular evolution of the tprC, D, I, K, G, and J genes in the pathogenic genus Treponema. Mol Biol Evol 23: 2220–2233. PubMed

Turner TB, Hollander DH (1957) 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 3–266. PubMed

Cox DL, Moeckli RA, Fieldsteel AH (1984) Cultivation of pathogenic treponema in tissue cultures of SflEp cells. In Vitro 20: 879–883. PubMed

Strouhal M, Smajs D, Matejkova P, Sodergren E, Amin AG, et al. (2007) Genome differences between Treponema pallidum subsp. pallidum strain Nichols and T. paraluiscuniculi strain Cuniculi A. Infect Immun 75: 5859–5866. PubMed PMC

Weinstock GM, Norris SJ, Sodergren E, Smajs D (2000) Identification of virulence genes in silico: Infection disease genomics. Virulence mechanisms of Bacterial Pathogens 378.

Garcia-Vallve S, Romeu A, Palau J (2000) Horizontal gene transfer in bacterial and archaeal complete genomes. Genome Res 10: 1719–1725. PubMed PMC

Smajs D, Mikalova L, Cejkova D, Strouhal M, Zobanikova M, et al.. (2011) Whole Genome Analyses of Treponemes: New Targets for Strain- and Subspecies-Specific Molecular Diagnostics. In: Sato NS, editor. Syphilis - Recognition, Description and Diagnosis: InTech. pp. 130.

Harper KN, Ocampo PS, Steiner BM, George RW, Silverman MS, et al. (2008) On the origin of the treponematoses: a phylogenetic approach. PLoS Negl Trop Dis 2: e148. PubMed PMC

Wang GC, Wang Y (1996) The frequency of chimeric molecules as a consequence of PCR co-amplification of 16S rRNA genes from different bacterial species. Microbiology 142 (Pt 5) 1107–1114. PubMed

Flasarova M, Pospisilova P, Mikalova L, Valisova Z, Dastychova E, et al. (2012) 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 PubMed

Smith JM, Dowson CG, Spratt BG (1991) Localized sex in bacteria. Nature 349: 29–31. PubMed

Feavers IM, Heath AB, Bygraves JA, Maiden MC (1992) Role of horizontal genetic exchange in the antigenic variation of the class 1 outer membrane protein of Neisseria meningitidis. Mol Microbiol 6: 489–495. PubMed

Kulick S, Moccia C, Didelot X, Falush D, Kraft C, et al. (2008) Mosaic DNA imports with interspersions of recipient sequence after natural transformation of Helicobacter pylori. PLoS One 3: e3797. PubMed PMC

Abastado JP, Cami B, Dinh TH, Igolen J, Kourilsky P (1984) Processing of complex heteroduplexes in Escherichia coli and Cos-1 monkey cells. Proc Natl Acad Sci U S A 81: 5792–5796. PubMed PMC

Centurion-Lara A, LaFond RE, Hevner K, Godornes C, Molini BJ, et al. (2004) Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection. Mol Microbiol 52: 1579–1596. PubMed

Kobayashi I (1992) Mechanisms for gene conversion and homologous recombination: the double-strand break repair model and the successive half crossing-over model. Adv Biophys 28: 81–133. PubMed

Seshadri R, Myers GS, Tettelin H, Eisen JA, Heidelberg JF, et al. (2004) Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes. Proc Natl Acad Sci U S A 101: 5646–5651. PubMed PMC

Walker EM, Arnett JK, Heath JD, Norris SJ (1991) Treponema pallidum subsp. pallidum has a single, circular chromosome with a size of approximately 900 kilobase pairs. Infect Immun 59: 2476–2479. PubMed PMC

Kuramitsu HK, Chi B, Ikegami A (2005) Genetic manipulation of Treponema denticola. Curr Protoc Microbiol Chapter 12: Unit 12B 12. PubMed

Hyde JA, Weening EH, Skare JT (2011) Genetic transformation of Borrelia burgdorferi. Curr Protoc Microbiol Chapter 12: Unit 12C 14. PubMed PMC

Tilly K, Elias AF, Bono JL, Stewart P, Rosa P (2000) DNA exchange and insertional inactivation in spirochetes. J Mol Microbiol Biotechnol 2: 433–442. PubMed

Miller JN (1973) Immunity in experimental syphilis. VI. Successful vaccination of rabbits with Treponema pallidum, Nichols strain, attenuated by -irradiation. J Immunol 110: 1206–1215. PubMed

Chan JK, Schell RF, Le Frock JL (1982) Mitogenic responses of hamsters infected with Treponema pertenue Lack of correlation with passive transfer of resistance. Br J Vener Dis 58: 292–297. PubMed PMC

Centurion-Lara A, Castro C, Castillo R, Shaffer JM, Van Voorhis WC, et al. (1998) The flanking region sequences of the 15-kDa lipoprotein gene differentiate pathogenic treponemes. J Infect Dis 177: 1036–1040. PubMed

Cameron CE, Castro C, Lukehart SA, Van Voorhis WC (1999) Sequence conservation of glycerophosphodiester phosphodiesterase among Treponema pallidum strains. Infect Immun 67: 3168–3170. PubMed PMC

Mansilla J, Rothschild BM, Pijoan C, Rothchild C (2000) Transitions among treponematoses in ancient Mexico. Chungará (Arica) 32.

de Melo FL, de Mello JC, Fraga AM, Nunes K, Eggers S (2010) Syphilis at the crossroad of phylogenetics and paleopathology. PLoS Negl Trop Dis 4: e575. PubMed PMC

Perine PL, Hopkins DR, Niemel PLA, St John RK, Causse G, et al.. (1984) Handbook of endemic treponematoses. Geneva: World Health Organization.

Cox DL, Luthra A, Dunham-Ems S, Desrosiers DC, Salazar JC, et al. (2010) Surface immunolabeling and consensus computational framework to identify candidate rare outer membrane proteins of Treponema pallidum. Infect Immun 78: 5178–5194. PubMed PMC

Desrosiers DC, Anand A, Luthra A, Dunham-Ems SM, LeDoyt M, et al. (2011) TP0326, a Treponema pallidum beta-barrel assembly machinery A (BamA) orthologue and rare outer membrane protein. Mol Microbiol 80: 1496–1515. PubMed PMC

Van Voorhis WC, Barrett LK, Lukehart SA, Schmidt B, Schriefer M, et al. (2003) Serodiagnosis of syphilis: antibodies to recombinant Tp0453, Tp92, and Gpd proteins are sensitive and specific indicators of infection by Treponema pallidum. J Clin Microbiol 41: 3668–3674. PubMed PMC

Brinkman MB, McKevitt M, McLoughlin M, Perez C, Howell J, et al. (2006) Reactivity of antibodies from syphilis patients to a protein array representing the Treponema pallidum proteome. J Clin Microbiol 44: 888–891. PubMed PMC

Cameron CE, Lukehart SA, Castro C, Molini B, Godornes C, et al. (2000) Opsonic potential, protective capacity, and sequence conservation of the Treponema pallidum subspecies pallidum Tp92. J Infect Dis 181: 1401–1413. PubMed

Greene SR, Stamm LV (1998) Molecular characterization of Treponema pallidum mcp2, a putative chemotaxis protein gene. Infect Immun 66: 2999–3002. PubMed PMC

Smajs D, McKevitt M, Howell JK, Norris SJ, Cai WW, et al. (2005) Transcriptome of Treponema pallidum: gene expression profile during experimental rabbit infection. J Bacteriol 187: 1866–1874. PubMed PMC

Anantharaman V, Aravind L (2000) Cache - a signaling domain common to animal Ca(2+)-channel subunits and a class of prokaryotic chemotaxis receptors. Trends Biochem Sci 25: 535–537. PubMed

Anand A, Luthra A, Dunham-Ems S, Caimano MJ, Karanian C, et al. (2012) TprC/D (Tp0117/131), a Trimeric, Pore-Forming Rare Outer Membrane Protein of Treponema pallidum, Has a Bipartite Domain Structure. J Bacteriol 194: 2321–2333. PubMed PMC

Morgan CA, Lukehart SA, Van Voorhis WC (2002) Immunization with the N-terminal portion of Treponema pallidum repeat protein K attenuates syphilitic lesion development in the rabbit model. Infect Immun 70: 6811–6816. PubMed PMC

Whole-genome sequencing reveals evidence for inter-species transmission of the yaws bacterium among nonhuman primates in Tanzania

Evolutionary Processes in the Emergence and Recent Spread of the Syphilis Agent, Treponema pallidum

Strain diversity of Treponema pallidum subsp. pertenue suggests rare interspecies transmission in African nonhuman primates

Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens

Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution

A public database for the new MLST scheme for Treponema pallidum subsp. pallidum: surveillance and epidemiology of the causative agent of syphilis

Complete genome sequences of two strains of Treponema pallidum subsp. pertenue from Indonesia: Modular structure of several treponemal genes

Nonhuman primates across sub-Saharan Africa are infected with the yaws bacterium Treponema pallidum subsp. pertenue

Sequencing of Treponema pallidum subsp. pallidum from isolate UZ1974 using Anti-Treponemal Antibodies Enrichment: First complete whole genome sequence obtained directly from human clinical material

Molecular characterization of Treponema pallidum subsp. pallidum in Switzerland and France with a new multilocus sequence typing scheme

Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of Treponema pallidum subsp. pallidum, the Syphilis Spirochete

Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively

Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen

A Retrospective Study on Genetic Heterogeneity within Treponema Strains: Subpopulations Are Genetically Distinct in a Limited Number of Positions

Macrolide Resistance in the Syphilis Spirochete, Treponema pallidum ssp. pallidum: Can We Also Expect Macrolide-Resistant Yaws Strains?

Whole genome sequence of the Treponema pallidum subsp. endemicum strain Bosnia A: the genome is related to yaws treponemes but contains few loci similar to syphilis treponemes

Resequencing of Treponema pallidum ssp. pallidum strains Nichols and SS14: correction of sequencing errors resulted in increased separation of syphilis treponeme subclusters

Whole genome sequence of the Treponema Fribourg-Blanc: unspecified simian isolate is highly similar to the yaws subspecies

Zobrazit více v PubMed

GENBANK
AE000520, CP000805, CP001752, CP002103, CP002374, CP002375, CP002376, CP003064, EU101896, EU101902, EU101910, EU101922, EU102075, EU102088, EU102098, EU102160, EU102170, JX392330, JX392331