1887

Abstract

, a human pathogen associated with sexually transmitted diseases, is unique in that it has the smallest genome of any known free-living organism. Despite its small genome, 4.7 % of the total genomic sequence is devoted to making the MgPa adhesin operon (containing the MG190, MG191 and MG192 genes) and its repetitive chromosomal sequences (known as MgPars). The goals of this study were to investigate the location, organization and variability of trinucleotide tandem repeats (TTRs) in the MgPa operon and MgPars and to explore the possible mechanisms and role of TTR variations. By analysing the complete MgPa operon and complete or partial MgPar sequences in a collection of 15 geographically diverse clinical strains of , TTR sequences were identified in four regions in MG191, one region in MG192, and two or three regions in each of all nine MgPars except for MgPar 3. These TTRs were variable not only in the repeat copy number but also in the repeat unit sequence among or within strains. The key mechanisms for the TTR variations likely include recombination between MgPa and MgPars, and slipped-strand mispairing. TTR variation may represent a mechanism to maximize the variation of the MgPa operon, which is complementary to genetic variation involving segmental recombination between MgPa and MgPars, thus enhancing the organism’s ability to adhere to and colonize host cells as well as evasion of the host immune system.

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2012-02-01
2019-12-14
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References

  1. Bowen S., Wheals A. E.. ( 2006;). Ser/Thr-rich domains are associated with genetic variation and morphogenesis in Saccharomyces cerevisiae. . Yeast 23:, 633–640. [CrossRef][PubMed]
    [Google Scholar]
  2. Charlesworth B., Sniegowski P., Stephan W.. ( 1994;). The evolutionary dynamics of repetitive DNA in eukaryotes. . Nature 371:, 215–220. [CrossRef][PubMed]
    [Google Scholar]
  3. Clausen H. F., Fedder J., Drasbek M., Nielsen P. K., Toft B., Ingerslev H. J., Birkelund S., Christiansen G.. ( 2001;). Serological investigation of Mycoplasma genitalium in infertile women. . Hum Reprod 16:, 1866–1874. [CrossRef][PubMed]
    [Google Scholar]
  4. Dallo S. F., Baseman J. B.. ( 1991;). Adhesin gene of Mycoplasma genitalium exists as multiple copies. . Microb Pathog 10:, 475–480. [CrossRef][PubMed]
    [Google Scholar]
  5. Di Prospero N. A., Fischbeck K. H.. ( 2005;). Therapeutics development for triplet repeat expansion diseases. . Nat Rev Genet 6:, 756–765. [CrossRef][PubMed]
    [Google Scholar]
  6. Fraser C. M., Gocayne J. D., White O., Adams M. D., Clayton R. A., Fleischmann R. D., Bult C. J., Kerlavage A. R., Sutton G.. & other authors ( 1995;). The minimal gene complement of Mycoplasma genitalium. . Science 270:, 397–403. [CrossRef][PubMed]
    [Google Scholar]
  7. Glass J. I., Assad-Garcia N., Alperovich N., Yooseph S., Lewis M. R., Maruf M., Hutchison C. A. III, Smith H. O., Venter J. C.. ( 2006;). Essential genes of a minimal bacterium. . Proc Natl Acad Sci U S A 103:, 425–430. [CrossRef][PubMed]
    [Google Scholar]
  8. Hall J., Hazlewood G. P., Huskisson N. S., Durrant A. J., Gilbert H. J.. ( 1989;). Conserved serine-rich sequences in xylanase and cellulase from Pseudomonas fluorescens subspecies cellulosa: internal signal sequence and unusual protein processing. . Mol Microbiol 3:, 1211–1219. [CrossRef][PubMed]
    [Google Scholar]
  9. Hamasuna R., Osada Y., Jensen J. S.. ( 2005;). Antibiotic susceptibility testing of Mycoplasma genitalium by TaqMan 5′ nuclease real-time PCR. . Antimicrob Agents Chemother 49:, 4993–4998. [CrossRef][PubMed]
    [Google Scholar]
  10. Hamasuna R., Osada Y., Jensen J. S.. ( 2007;). Isolation of Mycoplasma genitalium from first-void urine specimens by coculture with Vero cells. . J Clin Microbiol 45:, 847–850. [CrossRef][PubMed]
    [Google Scholar]
  11. Hjorth S. V., Björnelius E., Lidbrink P., Falk L., Dohn B., Berthelsen L., Ma L., Martin D. H., Jensen J. S.. ( 2006;). Sequence-based typing of Mycoplasma genitalium reveals sexual transmission. . J Clin Microbiol 44:, 2078–2083. [CrossRef][PubMed]
    [Google Scholar]
  12. Howard M. B., Ekborg N. A., Taylor L. E., Hutcheson S. W., Weiner R. M.. ( 2004;). Identification and analysis of polyserine linker domains in prokaryotic proteins with emphasis on the marine bacterium Microbulbifer degradans. . Protein Sci 13:, 1422–1425. [CrossRef][PubMed]
    [Google Scholar]
  13. Htun H., Dahlberg J. E.. ( 1989;). Topology and formation of triple-stranded H-DNA. . Science 243:, 1571–1576. [CrossRef][PubMed]
    [Google Scholar]
  14. Hu P. C., Schaper U., Collier A. M., Clyde W. A. Jr, Horikawa M., Huang Y. S., Barile M. F.. ( 1987;). A Mycoplasma genitalium protein resembling the Mycoplasma pneumoniae attachment protein. . Infect Immun 55:, 1126–1131.[PubMed]
    [Google Scholar]
  15. Iverson-Cabral S. L., Astete S. G., Cohen C. R., Rocha E. P., Totten P. A.. ( 2006;). Intrastrain heterogeneity of the mgpB gene in Mycoplasma genitalium is extensive in vitro and in vivo and suggests that variation is generated via recombination with repetitive chromosomal sequences. . Infect Immun 74:, 3715–3726. [CrossRef][PubMed]
    [Google Scholar]
  16. Iverson-Cabral S. L., Astete S. G., Cohen C. R., Totten P. A.. ( 2007;). mgpB and mgpC sequence diversity in Mycoplasma genitalium is generated by segmental reciprocal recombination with repetitive chromosomal sequences. . Mol Microbiol 66:, 55–73. [CrossRef][PubMed]
    [Google Scholar]
  17. Jensen J. S.. ( 2006;). Mycoplasma genitalium infections. Diagnosis, clinical aspects, and pathogenesis. . Dan Med Bull 53:, 1–27.[PubMed]
    [Google Scholar]
  18. Jensen J. S.. ( 2009;). Single-dose azithromycin treatment for Mycoplasma genitalium-positive urethritis: best but not good enough. . Clin Infect Dis 48:, 1655–1656. [CrossRef][PubMed]
    [Google Scholar]
  19. Jensen J. S., Hansen H. T., Lind K.. ( 1996;). Isolation of Mycoplasma genitalium strains from the male urethra. . J Clin Microbiol 34:, 286–291.[PubMed]
    [Google Scholar]
  20. Jensen J. S., Bradshaw C. S., Tabrizi S. N., Fairley C. K., Hamasuna R.. ( 2008;). Azithromycin treatment failure in Mycoplasma genitalium-positive patients with nongonococcal urethritis is associated with induced macrolide resistance. . Clin Infect Dis 47:, 1546–1553. [CrossRef][PubMed]
    [Google Scholar]
  21. Levinson G., Gutman G. A.. ( 1987;). Slipped-strand mispairing: a major mechanism for DNA sequence evolution. . Mol Biol Evol 4:, 203–221.[PubMed]
    [Google Scholar]
  22. Ma L., Martin D. H.. ( 2004;). Single-nucleotide polymorphisms in the rRNA operon and variable numbers of tandem repeats in the lipoprotein gene among Mycoplasma genitalium strains from clinical specimens. . J Clin Microbiol 42:, 4876–4878. [CrossRef][PubMed]
    [Google Scholar]
  23. Ma L., Jensen J. S., Myers L., Burnett J., Welch M., Jia Q., Martin D. H.. ( 2007;). Mycoplasma genitalium: an efficient strategy to generate genetic variation from a minimal genome. . Mol Microbiol 66:, 220–236. [CrossRef][PubMed]
    [Google Scholar]
  24. Ma L., Taylor S., Jensen J. S., Myers L., Lillis R., Martin D. H.. ( 2008;). Short tandem repeat sequences in the Mycoplasma genitalium genome and their use in a multilocus genotyping system. . BMC Microbiol 8:, 130. [CrossRef][PubMed]
    [Google Scholar]
  25. Ma L., Jensen J. S., Mancuso M., Hamasuna R., Jia Q., McGowin C. L., Martin D. H.. ( 2010;). Genetic variation in the complete MgPa operon and its repetitive chromosomal elements in clinical strains of Mycoplasma genitalium. . PLoS ONE 5:, e15660. [CrossRef][PubMed]
    [Google Scholar]
  26. McGowin C. L., Spagnuolo R. A., Pyles R. B.. ( 2010;). Mycoplasma genitalium rapidly disseminates to the upper reproductive tracts and knees of female mice following vaginal inoculation. . Infect Immun 78:, 726–736. [CrossRef][PubMed]
    [Google Scholar]
  27. Morrison-Plummer J., Lazzell A., Baseman J. B.. ( 1987;). Shared epitopes between Mycoplasma pneumoniae major adhesin protein P1 and a 140-kilodalton protein of Mycoplasma genitalium. . Infect Immun 55:, 49–56.[PubMed]
    [Google Scholar]
  28. Peterson S. N., Bailey C. C., Jensen J. S., Borre M. B., King E. S., Bott K. F., Hutchison C. A. III. ( 1995;). Characterization of repetitive DNA in the Mycoplasma genitalium genome: possible role in the generation of antigenic variation. . Proc Natl Acad Sci U S A 92:, 11829–11833. [CrossRef][PubMed]
    [Google Scholar]
  29. Richard G. F., Kerrest A., Dujon B.. ( 2008;). Comparative genomics and molecular dynamics of DNA repeats in eukaryotes. . Microbiol Mol Biol Rev 72:, 686–727. [CrossRef][PubMed]
    [Google Scholar]
  30. Rocha E. P., Blanchard A.. ( 2002;). Genomic repeats, genome plasticity and the dynamics of Mycoplasma evolution. . Nucleic Acids Res 30:, 2031–2042. [CrossRef][PubMed]
    [Google Scholar]
  31. Svenstrup H. F., Jensen J. S., Gevaert K., Birkelund S., Christiansen G.. ( 2006;). Identification and characterization of immunogenic proteins of Mycoplasma genitalium. . Clin Vaccine Immunol 13:, 913–922. [CrossRef][PubMed]
    [Google Scholar]
  32. Tully J. G., Cole R. M., Taylor-Robinson D., Rose D. L.. ( 1981;). A newly discovered mycoplasma in the human urogenital tract. . Lancet 317:, 1288–1291. [CrossRef][PubMed]
    [Google Scholar]
  33. van Belkum A., Scherer S., van Alphen L., Verbrugh H.. ( 1998;). Short-sequence DNA repeats in prokaryotic genomes. . Microbiol Mol Biol Rev 62:, 275–293.[PubMed]
    [Google Scholar]
  34. Verstrepen K. J., Jansen A., Lewitter F., Fink G. R.. ( 2005;). Intragenic tandem repeats generate functional variability. . Nat Genet 37:, 986–990. [CrossRef][PubMed]
    [Google Scholar]
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