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The complete sequence of the mucosal pathogen Ureaplasma urealyticum


The comparison of the genomes of two very closely related human mucosal pathogens, Mycoplasma genitalium and Mycoplasma pneumoniae, has helped define the essential functions of a self-replicating minimal cell, as well as what constitutes a mycoplasma. Here we report the complete sequence of a more distant phylogenetic relative of those bacteria, Ureaplasma urealyticum (parvum biovar), which is also a mucosal pathogen of humans. It is the third mycoplasma to be sequenced, and has the smallest sequenced prokaryotic genome except for M. genitalium. Although the U. urealyticum genome is similar to the two sequenced mycoplasma genomes1,2, features make this organism unique among mycoplasmas and all bacteria. Almost all ATP synthesis is the result of urea hydrolysis, which generates an energy-producing electrochemical gradient. Some highly conserved eubacterial enzymes appear not to be encoded by U. urealyticum, including the cell-division protein FtsZ, chaperonins GroES and GroEL, and ribonucleoside-diphosphate reductase. U. urealyticum has six closely related iron transporters, which apparently arose through gene duplication, suggesting that it has a kind of respiration system not present in other small genome bacteria The genome is only 25.5% G+C in nucleotide content, and the G+C content of individual genes may predict how essential those genes are to ureaplasma survival.

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Figure 1: Metabolic pathways and substrate transport in U. urealyticum.
Figure 2: Conservation of gene order among U. urealyticum, M. pneumoniae and M. genitalium.
Figure 3: Distribution of U. urealyticum and M. genitalium genes according to percentage G+C.


  1. Fraser, C. M. et al. The minimal gene complement of Mycoplasma genitalium. Science 270, 397–403 (1995).

    Article  ADS  CAS  Google Scholar 

  2. Himmelreich, R. et al. Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae. Nucleic Acids Res. 24, 4420–4429 (1996).

    Article  CAS  Google Scholar 

  3. Cassell, G. H., Waites, K. B., Watson, H. L., Crouse, D. T. & Harasawa, R. Ureaplasma urealyticum intrauterine infection: role in prematurity and disease in newborns. Clin. Microbiol. Rev. 6, 69–87 ( 1993).

    Article  CAS  Google Scholar 

  4. Bradbury, J. M. International Committee on Systematic Bacteriology Subcommittee on Mollicutes: Minutes of the Interim Meeting 12 and 18 July 1996. Orlando, Florida, USA. Int. J. System. Bacteriol. 47, 911– 914 (1997).

    Article  Google Scholar 

  5. Smith, D. G., Russell, W. C., Ingledew, W. J. & Thirkell, D. Hydrolysis of urea by Ureaplasma urealyticum generates a transmembrane potential with resultant ATP synthesis. J. Bacteriol. 175, 3253–3258 (1993).

    Article  CAS  Google Scholar 

  6. Shepard, M. C. Human mycoplasma infections. Health Laboratory Science 3, 163–169 (1966).

    CAS  PubMed  Google Scholar 

  7. Mobley, H. L., Island, M. D. & Hausinger, R. P. Molecular biology of microbial ureases. Microbiol. Rev. 59, 451–480 (1985).

    Google Scholar 

  8. Romano, N., La Licata, R. & Russo Alesi, D. Energy production in Ureaplasma urealyticum. Pediatr. Infect. Dis. 5, 308– 312 (1986).

    Article  Google Scholar 

  9. Neyrolles, O., Ferris, S., Behbahani, N., Montagnier, L. & Blanchard, A. Organization of Ureaplasma urealyticum urease gene cluster and expression in a suppressor strain of Escherichia coli. J. Bacteriol. 178, 647–655 (1996).

    Article  CAS  Google Scholar 

  10. Smith, R. L., Thompson, L. J. & Maguire, M. E. Cloning and characterization of MgtE, a putative new class of Mg2+ transporter from Bacillus firmus OF4. J. Bacteriol. 177, 1233– 1238 (1995).

    Article  CAS  Google Scholar 

  11. Siewe, R. M. et al. Functional and genetic characterization of the (methyl)ammonium uptake carrier of Corynebacterium glutamicum. J. Biol. Chem. 271, 5398–5403 (1996).

    Article  CAS  Google Scholar 

  12. Jayakumar, A., Epstein, W. & Barnes, E. M. J. Characterization of ammonium (methylammonium)/potassium antiport in Escherichia coli. J. Biol. Chem. 260, 7528–7532 (1985).

    CAS  PubMed  Google Scholar 

  13. Soupene, E., He, L. D. Y. & Kustu, S. Ammonia acquisition in enteric bacteria: physiological role of the ammonium/methylammonium transport B (AmtB) protein. Proc. Natl Acad. Sci. USA 95, 7030– 7034 (1998).

    Article  ADS  CAS  Google Scholar 

  14. Bauminger, E. R. et al. Iron storage in Mycoplasma capricolum. J. Bacteriol. 141, 378–381 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Pollack, J. D., Merola, A. J., Platz, M. & Booth, R. L. J. Respiration-associated components of Mollicutes. J. Bacteriol. 146, 907–913 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Pollack, J. D., Williams, M. V. & McElhaney, R. N. The comparative metabolism of the mollicutes (Mycoplasmas): the utility for taxonomic classification and the relationship of putative gene annotation and phylogeny to enzymatic function in the smallest free-living cells. Crit. Rev. Microbiol. 23, 269– 354 (1997).

    Article  CAS  Google Scholar 

  17. Ligon, J. V. & Kenny, G. E. Virulence of ureaplasmal urease for mice. Infect. Immun. 59, 1170– 1171 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kilian, M., Brown, M. B., Brown, T. A., Freundt, E. A. & Cassell, G. H. Immunoglobulin A1 protease activity in strains of Ureaplasma urealyticum. Acta Pathol. Microbiol. Scand. B 92, 61–64 ( 1984).

    CAS  Google Scholar 

  19. De Silva, N. S. & Quinn, P. A. Localization of endogenous activity of phospholipases A and C in Ureaplasma urealyticum . J. Clin. Microbiol. 29, 1498– 1503 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Zheng, X. et al. Small repeating units within the Ureaplasma urealyticum MB antigen gene encode serovar specificity and are associated with antigen size variation. Infect. Immun. 63, 891– 898 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Upton, C. & Buckley, J. T. A new family of lipolytic enzymes? Trends Biochem. Sci. 20, 178– 179 (1995).

    Article  CAS  Google Scholar 

  22. Somerson, N. L., Walls, B. E. & Chanock, R. M. Hemolysin of Mycoplasma pneumoniae: tentative identification as a peroxide. Science 150, 226–228 (1965).

    Article  ADS  CAS  Google Scholar 

  23. Shepard, M. C. & Masover, M. C. in The Mycoplasmas (eds Barile, M. F. & Razin, S.) 451–494 (Academic, New York, 1979).

    Book  Google Scholar 

  24. Wren, B. W. et al. Characterization of a haemolysin from Mycobacterium tuberculosis with homology to a virulence factor of Serpulina hyodysenteriae. Microbiology 144, 1205– 1211 (1998).

    Article  CAS  Google Scholar 

  25. Himmelreich, R., Plagen, H., Hilbert, H., Reiner, B. & Herrmann, R. Comparative analysis of the genomes of the bacteria Mycoplasma pneumoniae and Mycoplasma genitalium. Nucleic Acids Res. 25, 701–712 ( 1997).

    Article  CAS  Google Scholar 

  26. Hutchison, C. A. et al. Global transposon mutagenesis and a minimal mycoplasma genome. Science 288, 2165–2169 (1999).

    Article  Google Scholar 

  27. Williams, M. V. & Pollack, J. D. in DNA Replication and Mutagenesis (eds Moses, R. C. & Summers, W. C.) 440– 444 (American Society for Microbiology, Washington DC, 1988).

    Google Scholar 

  28. Williams, M. V. & Pollack, J. D. A mollicute (mycoplasma) DNA repair enzyme: purification and characterization of uracil-DNA glycosylase. J. Bacteriol. 172, 2979– 2985 (1990).

    Article  CAS  Google Scholar 

  29. Chen, E. Y., Schlessinger, D. & Kere, J. Ordered shotgun sequencing, a strategy for integrated mapping and sequencing of YAC clones. Genomics 17, 651–656 (1993).

    Article  CAS  Google Scholar 

  30. Heiner, C. R., Hunkapiller, K. L., Chen, S. M., Glass, J. I. & Chen, E. Y. Sequencing multimegabase-template DNA with BigDye terminator chemistry. Genome Res. 8 , 557–561 (1998).

    Article  CAS  Google Scholar 

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The authors thank D. Schlessinger for establishing the collaboration that led to this project, Y. Hale for growing the U. urealyticum; R. Belo, P. Babayan, K. Hunkapiller and T. Nguyen for assistance with DNA sequencing; and C.-N. Chen, S. Peterson, K. Ketchum and S. Payne for helpful disscussions. This work was supported by PE Biosystems, the National Institute Allergy and Infectious Diseases of the National Institutes of Health, Eli Lilly and Company, and the University of Alabama at Birmingham, Department of Microbiology.

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Glass, J., Lefkowitz, E., Glass, J. et al. The complete sequence of the mucosal pathogen Ureaplasma urealyticum . Nature 407, 757–762 (2000).

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