Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84) affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9%) of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits) during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies.

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

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Graves S, Downes J. Experimental infection of man with rabbit-virulent Treponema paraluis-cuniculi. Br J Vener Dis. 1981;57:7–10. PubMed PMC

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

Jacobsthal E. Untersuchungen über eine syphilisähnliche Spontanerkrankung des Kaninchens (Paralues-cuniculi). Derm Wschr. 1920;71:569–571.

Smith JL, Pesetsky BR. The current status of Treponema cuniculi: Review of the literature. Br J Vener Dis. 1967;43:117–127. PubMed PMC

DiGiacomo RF, Talburt CD, Lukehart SA, Baker-Zander SA, Condon J. Treponema paraluis-cuniculi infection in a commercial rabbitry: epidemiology and serodiagnosis. Lab Anim Sci. 1983;33:562–566. PubMed

DiGiacomo RF, Lukehart SA, Talburt CD, Baker-Zander SA, Condon J, et al. Clinical course and treatment of venereal spirochaetosis in New Zealand white rabbits. Br J Vener Dis. 1984;60:214–218. PubMed PMC

Schell RF, Azadegan AA, Nitskansky SG, Lefrock JL. Acquired resistance of hamsters to challenge with homologous and heterologous virulent treponemes. Infect Immun. 1982;37:617–621. PubMed PMC

Turner TB, Hollander DH. Geneva: World Health Organization; 1957. Biology of the treponematoses.272 PubMed

Baker-Zander SA, Lukehart SA. Antigenic cross-reactivity between Treponema pallidum and other pathogenic members of the family Spirochaetaceae. Infect Immun. 1984;46:116–121. PubMed PMC

Hougen KH, Birch-Andersen A, Jensen HJ. Electron microscopy of Treponema cuniculi. Acta Pathol Microbiol Scand Microbiol Immunol. 1973;81:15–28. PubMed

Norris SJ, Pope V, Johnson RE, Larsen SA. Treponema and other human host-associated spirochetes. In: Murray PR, Baron EJ, Pfaller MA, Jorgensen JH, Yolken RH, editors. Manual of Clinical Microbiology. Washington DC: ASM Press; 2003. pp. 955–971.

Peeling RW, Hook EW. The pathogenesis of syphilis: the Great Mimicker, revisited. J Pathol. 2006;208:224–232. PubMed

Digiacomo RF, Lukehart SA, Talburt CD, Baker-Zander SA, Giddens WE, et al. Chronicity of infection with Treponema paraluis-cuniculi in New Zealand white rabbits. Genitourin Med. 1985;61:156–164. PubMed PMC

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.

Khan AS, Nelson RAJ, Turner TB. Immunological relationships among species and strains of virulent treponemes as determined with the treponemal immobilization test. Am J Hyg. 1951;53:296–316. PubMed

Giacani L, Sun ES, Hevner K, Molini BJ, Van Voorhis WC, et al. Tpr homologs in Treponema paraluiscuniculi Cuniculi A strain. Infect Immun. 2004;72:6561–6576. PubMed PMC

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

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

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

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

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

McKevitt M, Brinkman MB, McLoughlin M, Perez C, Howell JK, et al. Genome scale identification of Treponema pallidum antigens. Infect Immun. 2005;73:4445–4450. PubMed PMC

Setubal JC, Reis M, Matsunaga J, Haake DA. Lipoprotein computational prediction in spirochaetal genomes. Microbiology. 2006;152:113–121. PubMed PMC

Fenno J, Müller KH, McBride BC. Sequence analysis, expression, and binding activity of recombinant major outer sheath protein (Msp) of Treponema denticola. J Bacteriol. 1996;178:2489–2497. PubMed PMC

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

Brinkman MB, McGill MA, Pettersson J, Rogers A, Matejkova P, et al. A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin. Infect Immun. 2008;76:1848–1857. PubMed PMC

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. PubMed

Šmajs D, McKevitt M, Wang L, Howell JK, Norris SJ, et al. BAC library of T. pallidum DNA in E. coli. Genome Res. 2002;12:515–522. PubMed PMC

Titz B, Rajagopala SV, Goll J, Häuser R, McKevitt MT, et al. The Binary protein interactome of Treponema pallidum - the syphilis spirochete. PLoS One. 2008;3:e2292. PubMed PMC

Centurion-Lara A, Castro C, Barrett L, Cameron C, Mostowfi M, et al. 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. PubMed PMC

Centurion-Lara A, Godornes C, Castro C, Van Voorhis WC, Lukehart SA. The tprK gene is heterogeneous among Treponema pallidum strains and has multiple alleles. Infect Immun. 2000a;68:824–831. PubMed PMC

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

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

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. PubMed PMC

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

Morozov V, Mushegian AR, Koonin EV, Bork P. A putative nucleic acid-binding domain in Bloom's and Werner's syndrome helicases. Trends in Biochem Sci. 1997;22:417–418. PubMed

Bernstein DA, Keck JL. Domain mapping of Escherichia coli RecQ defines the roles of conserved N- and C-terminal regions in the RecQ family. Nucleic Acids Res. 2003;31:2778–2785. PubMed PMC

Stohl EA, Brockman JP, Burkle KL, Morimatsu K, Kowalczykowski SC, et al. Escherichia coli RecX inhibits RecA recombinase and coprotease activities in vitro and in vivo. J Biol Chem. 2003;278:2278–2285. PubMed

Stohl EA, Seifert HS. The recX gene potentiates homologous recombination in Neisseria gonorrhoeae. Mol Microbiol. 2001;40:1301–1310. PubMed

Noonan JP, Grimwood J, Schmutz J, Dickson M, Myers RM. Gene conversion and the evolution of protocadherin gene cluster diversity. Genome Res. 2004;14:354–366. PubMed PMC

Harper KN, Liu H, Ocampo PS, Steiner BM, Martin A, et al. The sequence of the acidic repeat protein (arp) gene differentiates 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. PubMed

Pallen MJ, Wren BW. Bacterial pathogenomics. Nature. 2007;449:835–842. PubMed

Baseman JB, Nichols JC, Rumpp JW, Hayes NS. Purification of Treponema pallidum from infected rabbit tissue: resolution into two treponemal populations. Infect Immun. 1974;10:1062–1067. PubMed PMC

Zerbino DR, Birney E. Velvet: Algorithms for de novo short read assembly using de Bruijn graphs. Genome Res. 2008;18:821–829. PubMed PMC

Weinstock GM, Norris SJ, Sodergren E, Smajs D. Identification of virulence genes in silico: infectious disease genomics. In: Brogden KA, Roth JA, Stanton TB, Bolin CA, Minion FC, Wannemuehler MJ, editors. Virulence mechanisms of bacterial pathogens. Washington, DC: ASM Press; 2000. pp. 251–261.

Nelson KE, Weinstock GM, Highlander SK, Worley KC, Creasy HH, et al. A Catalog of Reference Genomes from the Human Microbiome. Science. 2010;328:994–999. PubMed PMC

Delcher A, Harmon D, Kasif S, White O, Salzberg SL. Improved microbial gene identification with GLIMMER. Nucleic Acids Res. 1999;27:4636–4641. PubMed PMC

Lukashin AV, Borodovsky M. GeneMark.hmm: new solutions for gene finding. Nucleic Acids Res. 1998;26:1107–1115. PubMed PMC

Gordon D, Abajian C, Green P. Consed: A graphical tool for sequence finishing. Genome Res. 1998;8:195–202. PubMed

Librado P, Rozas J. DnaSP v5: A software for comprehensive analysis of DNA polymorphism data. Bioinformatics. 2009;25:1451–1452. PubMed

Nei M, Kumar S. New York: Oxford University Press; 2000. Molecular Evolution and Phylogenetics. (333 pp)

Tamura K, Dudley J, Nei M, Kumar S. MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol. 2007;24:1596–1599. PubMed

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