1887

Abstract

We present the complete genomic sequence of , an organism suggested to be associated with the pathogenesis of rheumatoid arthritis in humans. The genome is composed of 977 524 bp and has a mean G+C content of 26.95 mol%. There are 835 predicted protein-coding sequences and a mean coding density of 87.6 %. Functions have been assigned to 58.8 % of the predicted protein-coding sequences, while 18.4 % of the proteins are conserved hypothetical proteins and 22.8 % are hypothetical proteins. In addition, there are two complete rRNA operons and 36 tRNA coding sequences. The largest gene families are the ABC transporter family (42 members), and the functionally heterogeneous group of lipoproteins (28 members), which encode the characteristic prokaryotic cysteine ‘lipobox’. Protein secretion occurs through a pathway consisting of SecA, SecD, SecE, SecG, SecY and YidC. Some highly conserved eubacterial proteins, such as GroEL and GroES, are notably absent. The genes encoding DnaK-DnaJ-GrpE and Tig, forming the putative complex of chaperones, are intact, providing the only known control over protein folding. Eighteen nucleases and 17 proteases and peptidases were detected as well as three genes for the thioredoxin-thioreductase system. Overall, this study presents insights into the physiology of , and provides several examples of the genetic basis of systems that might function as virulence factors in this organism.

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2011-03-01
2020-11-30
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References

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. 1990; Basic local alignment search tool. J Mol Biol 215:403–410
    [Google Scholar]
  2. Altschul S. F., Madden T. L., Schaffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. 1997; Gapped blast and psi-blast: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402
    [Google Scholar]
  3. Ben-Menachem G., Himmelreich R., Herrmann R., Aharonowitz Y., Rottem S. 1997; The thioredoxin reductase system of mycoplasmas. Microbiology 143:1933–1940
    [Google Scholar]
  4. Bradford M. M. 1976; A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
    [Google Scholar]
  5. Brusilow W. S., Porter A. C., Simoni R. D. 1983; Cloning and expression of uncI , the first gene of the unc operon of Escherichia coli . J Bacteriol 155:1265–1270
    [Google Scholar]
  6. Calcutt M. J., Lavrrar J. L., Wise K. S. 1999; IS 1630 of Mycoplasma fermentans , a novel IS 30 -type insertion element that targets and duplicates inverted repeats of variable length and sequence during insertion. J Bacteriol 181:7597–7607
    [Google Scholar]
  7. Calcutt M. J., Lewis M. S., Wise K. S. 2002; Molecular genetic analysis of ICEF, an integrative conjugal element that is present as a repetitive sequence in the chromosome of Mycoplasma fermentans PG18. J Bacteriol 184:6929–6941
    [Google Scholar]
  8. Carver T., Berriman M., Tivey A., Patel C., Bohme U., Barrell B. G., Parkhill J., Rajandream M. A. 2008; Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database. Bioinformatics 24:2672–2676
    [Google Scholar]
  9. Chambaud I., Wroblewski H., Blanchard A. 1999; Interactions between mycoplasma lipoproteins and the host immune system. Trends Microbiol 7:493–499
    [Google Scholar]
  10. Chambaud I., Heilig R., Ferris S., Barbe V., Samson D., Galisson F., Moszer I., Dybvig K., Wróblewski H.other authors 2001; The complete genome sequence of the murine respiratory pathogen Mycoplasma pulmonis . Nucleic Acids Res 29:2145–2153
    [Google Scholar]
  11. Chang L. J., Chen W. H., Minion F. C., Shiuan D. 2008; Mycoplasmas regulate the expression of heat-shock protein genes through CIRCE–HrcA interactions. Biochem Biophys Res Commun 367:213–218
    [Google Scholar]
  12. Chopra-Dewasthaly R., Citti C., Glew M. D., Zimmermann M., Rosengarten R., Jechlinger W. 2008; Phase-locked mutants of Mycoplasma agalactiae : defining the molecular switch of high-frequency Vpma antigenic variation. Mol Microbiol 67:1196–1210
    [Google Scholar]
  13. Dandekar T., Huynen M., Regula J. T., Ueberle B., Zimmermann C. U., Andrade M. A., Doerks T., Sánchez-Pulido L., Snel B. other authors 2000; Re-annotating the Mycoplasma pneumoniae genome sequence: adding value, function and reading frames. Nucleic Acids Res 28:3278–3288
    [Google Scholar]
  14. Deutsch J., Salman M., Rottem S. 1995; An unusual polar lipid from the cell membrane of Mycoplasma fermentans . Eur J Biochem 227:897–902
    [Google Scholar]
  15. Dimitrov D. S., Franzoso G., Salman M., Blumenthal R., Tarshis M., Barile M. F., Rottem S. 1993; Mycoplasma fermentans (incognitus strain) cells are able to fuse with T lymphocytes. Clin Infect Dis 17:Suppl. 1S305–S308
    [Google Scholar]
  16. Donnan F. G. 1911; Theorie der Membrangleichgewichte und Membranpotentiale bei Vorhandensein von nicht dialysierenden Elektrolyten. Z Elektrochemie 17:572–581
    [Google Scholar]
  17. Dybvig K., Zuhua C., Lao P., Jordan D. S., French C. T., Tu A. H., Loraine A. E. 2008; Genome of Mycoplasma arthritidis . Infect Immun 76:4000–4008
    [Google Scholar]
  18. Franzoso G., Dimitrov D. S., Blumenthal R., Barile M. F., Rottem S. 1992; Fusion of Mycoplasma fermentans strain incognitus with T-lymphocytes. FEBS Lett 303:251–254
    [Google Scholar]
  19. 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
    [Google Scholar]
  20. Futai M., Noumi T., Maeda M. 1989; ATP synthase (H+-ATPase): results by combined biochemical and molecular biological approaches. Annu Rev Biochem 58:111–136
    [Google Scholar]
  21. Glass J. I., Lefkowitz E. J., Glass J. S., Heiner C. R., Chen E. Y., Cassell G. H. 2000; The complete sequence of the mucosal pathogen Ureaplasma urealyticum . Nature 407:757–762
    [Google Scholar]
  22. 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
    [Google Scholar]
  23. Groth G. 2000; Molecular models of the structural arrangement of subunits and the mechanism of proton translocation in the membrane domain of F1F0 ATP synthase. Biochim Biophys Acta 1458417–427
    [Google Scholar]
  24. Haier J., Nasralla M., Franco A. R., Nicolson G. L. 1999; Detection of mycoplasmal infections in blood of patients with rheumatoid arthritis. Rheumatology (Oxford 38:504–509
    [Google Scholar]
  25. Hall R. E., Agarwal S., Kestler D. P., Cobb J. A., Goldstein K. M., Chang N. S. 1996; cDNA and genomic cloning and expression of the P48 monocytic differentiation/activation factor, a Mycoplasma fermentans gene product. Biochem J 319:919–927
    [Google Scholar]
  26. Hallamaa K. M., Browning G. F., Tang S. L. 2006; Lipoprotein multigene families in Mycoplasma pneumoniae . J Bacteriol 188:5393–5399
    [Google Scholar]
  27. Hansen F. G., Nielsen J., Riise E., von Meyenburg K. 1981; The genes for the eight subunits of the membrane bound ATP synthase of Escherichia coli . Mol Gen Genet 183:463–472
    [Google Scholar]
  28. Hantke K., Braun V. 1973; Covalent binding of lipid to protein. Diglyceride and amide-linked fatty acid at the N-terminal end of the murein-lipoprotein of the Escherichia coli outer membrane. Eur J Biochem 34:284–296
    [Google Scholar]
  29. Hayflick L. 1965; Tissue cultures and mycoplasmas. Tex Rep Biol Med 23:Suppl. 1285
    [Google Scholar]
  30. Himmelreich R., Hilbert H., Plagens H., Pirkl E., Li B. C., Herrmann R. 1996; Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae . Nucleic Acids Res 24:4420–4449
    [Google Scholar]
  31. Holland I. B., Blight M. A. 1999; ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans. J Mol Biol 293:381–399
    [Google Scholar]
  32. Horino A., Kenri T., Sasaki Y., Okamura N., Sasaki T. 2009; Identification of a site-specific tyrosine recombinase that mediates promoter inversions of phase-variable mpl lipoprotein genes in Mycoplasma penetrans . Microbiology 155:1241–1249
    [Google Scholar]
  33. Horowitz S., Evinson B., Borer A., Horowitz J. 2000; Mycoplasma fermentans in rheumatoid arthritis and other inflammatory arthritides. J Rheumatol 27:2747–2753
    [Google Scholar]
  34. Hu W. S., Wang R. Y., Liou R. S., Shih J. W., Lo S. C. 1990; Identification of an insertion-sequence-like genetic element in the newly recognized human pathogen Mycoplasma incognitus . Gene 93:67–72
    [Google Scholar]
  35. Ishida N., Irikura D., Matsuda K., Sato S., Sone T., Tanaka M., Asano K. 2009; Molecular cloning and expression of a novel cholinephosphotransferase involved in glycoglycerophospholipid biosynthesis of Mycoplasma fermentans . Curr Microbiol 58:535–540
    [Google Scholar]
  36. Jaffe J. D., Stange-Thomann N., Smith C., DeCaprio D., Fisher S., Butler J., Calvo S., Elkins T., FitzGerald M. G. other authors 2004; The complete genome and proteome of Mycoplasma mobile . Genome Res 14:1447–1461
    [Google Scholar]
  37. Johnson S., Sidebottom D., Bruckner F., Collins D. 2000; Identification of Mycoplasma fermentans in synovial fluid samples from arthritis patients with inflammatory disease. J Clin Microbiol 38:90–93
    [Google Scholar]
  38. Junge W., Panke O., Cherepanov D. A., Gumbiowski K., Muller M., Engelbrecht S. 2001; Inter-subunit rotation and elastic power transmission in F0F1-ATPase. FEBS Lett 504:152–160
    [Google Scholar]
  39. Kawahito Y., Ichinose S., Sano H., Tsubouchi Y., Kohno M., Yoshikawa T., Tokunaga D., Hojo T., Harasawa R. other authors 2008; Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis. Biochem Biophys Res Commun 369:561–566
    [Google Scholar]
  40. Klein P., Somorjai R. L., Lau P. C. 1988; Distinctive properties of signal sequences from bacterial lipoproteins. Protein Eng 2:15–20
    [Google Scholar]
  41. Koonin E. V. 2000; How many genes can make a cell: the minimal-gene-set concept. Annu Rev Genomics Hum Genet 1:99–116
    [Google Scholar]
  42. Kuwahara T., Yamashita A., Hirakawa H., Nakayama H., Toh H., Okada N., Kuhara S., Hattori M., Hayashi T., Ohnishi Y. 2004; Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation. Proc Natl Acad Sci U S A 101:14919–14924
    [Google Scholar]
  43. Leigh S. A., Wise K. S. 2002; Identification and functional mapping of the Mycoplasma fermentans P29 adhesin. Infect Immun 70:4925–4935
    [Google Scholar]
  44. Lobry J. R. 1996; Asymmetric substitution patterns in the two DNA strands of bacteria. Mol Biol Evol 13:660–665
    [Google Scholar]
  45. Lysnyansky I., Calcutt M. J., Ben-Barak I., Ron Y., Levisohn S., Methe B. A., Yogev D. 2009; Molecular characterization of newly identified IS 3 , IS 4 and IS 30 insertion sequence-like elements in Mycoplasma bovis and their possible roles in genome plasticity. FEMS Microbiol Lett 294:172–182
    [Google Scholar]
  46. Mahillon J., Leonard C., Chandler M. 1999; IS elements as constituents of bacterial genomes. Res Microbiol 150:675–687
    [Google Scholar]
  47. Maniloff J. 2002; Phylogeny and evolution. In Molecular Biology and Pathogenicity of Mycoplasmas pp 31–43 Edited by Razin S., Herrmann R. New York: Kluwer Academic/Plenum Publishers;
    [Google Scholar]
  48. Matsuda K., Kasama T., Ishizuka I., Handa S., Yamamoto N., Taki T. 1994; Structure of a novel phosphocholine-containing glycoglycerolipid from Mycoplasma fermentans . J Biol Chem 269:33123–33128
    [Google Scholar]
  49. Minion F. C., Lefkowitz E. J., Madsen M. L., Cleary B. J., Swartzell S. M., Mahairas G. G. 2004; The genome sequence of Mycoplasma hyopneumoniae strain 232, the agent of swine mycoplasmosis. J Bacteriol 186:7123–7133
    [Google Scholar]
  50. Mühlradt P. F., Schade U. 1991; MDHM, a macrophage-stimulatory product of Mycoplasma fermentans , leads to in vitro interleukin-1 (IL-1), IL-6, tumor necrosis factor, and prostaglandin production and is pyrogenic in rabbits. Infect Immun 59:3969–3974
    [Google Scholar]
  51. Nouvel L. X., Sirand-Pugnet P., Marenda M. S., Sagné E., Barbe V., Mangenot S., Schenowitz C., Jacob D., Barré A.other authors 2010; Comparative genomic and proteomic analyses of two Mycoplasma agalactiae strains: clues to the macro- and micro-events that are shaping mycoplasma diversity. BMC Genomics 11:86
    [Google Scholar]
  52. Okusawa T., Fujita M., Nakamura J., Into T., Yasuda M., Yoshimura A., Hara Y., Hasebe A., Golenbock D. T. other authors 2004; Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by Toll-like receptors 2 and 6. Infect Immun 72:1657–1665
    [Google Scholar]
  53. Olson L. D., Renshaw C. A., Rottem S., Boal J. H. 1993; Arginine utilization by Mycoplasma fermentans is not regulated by glucose metabolism: a 13C-NMR study. FEMS Microbiol Lett 108:47–52
    [Google Scholar]
  54. Overbeek R., Larsen N., Walunas T., D'Souza M., Pusch G., Selkov E. Jr, Liolios K., Joukov V., Kaznadzey D. other authors 2003; The ERGO genome analysis and discovery system. Nucleic Acids Res 31:164–171
    [Google Scholar]
  55. Papazisi L., Gorton T. S., Kutish G., Markham P. F., Browning G. F., Nguyen D. K., Swartzell S., Madan A., Mahairas G., Geary S. J. 2003; The complete genome sequence of the avian pathogen Mycoplasma gallisepticum strain R(low. Microbiology 149:2307–2316
    [Google Scholar]
  56. Pereyre S., Sirand-Pugnet P., Beven L., Charron A., Renaudin H., Barré A., Avenaud P., Jacob D., Couloux A. other authors 2009; Life on arginine for Mycoplasma hominis : clues from its minimal genome and comparison with other human urogenital mycoplasmas. PLoS Genet 5:e1000677
    [Google Scholar]
  57. Pyrowolakis G., Hofmann D., Herrmann R. 1998; The subunit b of the F0F1-type ATPase of the bacterium Mycoplasma pneumoniae is a lipoprotein. J Biol Chem 273:24792–24796
    [Google Scholar]
  58. Raetz C. R., Dowhan W. 1990; Biosynthesis and function of phospholipids in Escherichia coli . J Biol Chem 265:1235–1238
    [Google Scholar]
  59. Rasmussen O. F., Shirvan M. H., Margalit H., Christiansen C., Rottem S. 1992; Nucleotide sequence, organization and characterization of the atp genes and the encoded subunits of Mycoplasma gallisepticum ATPase. Biochem J 285:881–888
    [Google Scholar]
  60. Razin S. 1992; Peculiar properties of mycoplasmas: the smallest self-replicating prokaryotes. FEMS Microbiol Lett 79:423–431
    [Google Scholar]
  61. Razin S., Yogev D., Naot Y. 1998; Molecular biology and pathogenicity of mycoplasmas. Microbiol Mol Biol Rev 62:1094–1156
    [Google Scholar]
  62. Röske K., Calcutt M. J., Wise K. S. 2004; The Mycoplasma fermentans prophage phiMFV1: genome organization, mobility and variable expression of an encoded surface protein. Mol Microbiol 52:1703–1720
    [Google Scholar]
  63. Rottem S. 1980; Membrane lipids of mycoplasmas. Biochim Biophys Acta 604:65–90
    [Google Scholar]
  64. Rottem S. 2003; Interaction of mycoplasmas with host cells. Physiol Rev 83:417–432
    [Google Scholar]
  65. Rottem S., Naot Y. 1998; Subversion and exploitation of host cells by mycoplasmas. Trends Microbiol 6:436–440
    [Google Scholar]
  66. Ruiter M., Wentholt H. M. 1952; The occurrence of a pleuropneumonia-like organism in fuso-spirillary infections of the human genital mucosa. J Invest Dermatol 18:313–325
    [Google Scholar]
  67. Sasaki Y., Ishikawa J., Yamashita A., Oshima K., Kenri T., Furuya K., Yoshino C., Horino A., Shiba T. other authors 2002; The complete genomic sequence of Mycoplasma penetrans , an intracellular bacterial pathogen in humans. Nucleic Acids Res 30:5293–5300
    [Google Scholar]
  68. Schaeverbeke T., Gilroy C. B., Bebear C., Dehais J., Taylor-Robinson D. 1996; Mycoplasma fermentans in joints of patients with rheumatoid arthritis and other joint disorders. Lancet 347:1418
    [Google Scholar]
  69. Schaeverbeke T., Clerc M., Lequen L., Charron A., Bebear C., de Barbeyrac B., Bannwarth B., Dehais J. 1998; Genotypic characterization of seven strains of Mycoplasma fermentans isolated from synovial fluids of patients with arthritis. J Clin Microbiol 36:1226–1231
    [Google Scholar]
  70. Shirvan M. H., Rottem S. 1993; Ion pumps and volume regulation in mycoplasma. Subcell Biochem 20:261–292
    [Google Scholar]
  71. Sirand-Pugnet P., Lartigue C., Marenda M., Jacob D., Barré A., Barbe V., Schenowitz C., Mangenot S., Couloux A. other authors 2007; Being pathogenic, plastic, and sexual while living with a nearly minimal bacterial genome. PLoS Genet 3:e75
    [Google Scholar]
  72. Sitaraman R., Denison A. M., Dybvig K. 2002; A unique, bifunctional site-specific DNA recombinase from Mycoplasma pulmonis . Mol Microbiol 46:1033–1040
    [Google Scholar]
  73. Staden R., Beal K. F., Bonfield J. K. 2000; The Staden package, 1998. Methods Mol Biol 132:115–130
    [Google Scholar]
  74. Tatusov R. L., Koonin E. V., Lipman D. J. 1997; A genomic perspective on protein families. Science 278:631–637
    [Google Scholar]
  75. Tech M., Merkl R. 2003; YACOP: enhanced gene prediction obtained by a combination of existing methods. In Silico Biol 3:441–451
    [Google Scholar]
  76. Theiss P., Karpas A., Wise K. S. 1996; Antigenic topology of the P29 surface lipoprotein of Mycoplasma fermentans : differential display of epitopes results in high-frequency phase variation. Infect Immun 64:1800–1809
    [Google Scholar]
  77. Thomas A., Linden A., Mainil J., Bischof D. F., Frey J., Vilei E. M. 2005; Mycoplasma bovis shares insertion sequences with Mycoplasma agalactiae and Mycoplasma mycoides subsp. mycoides SC: evolutionary and developmental aspects. FEMS Microbiol Lett 245:249–255
    [Google Scholar]
  78. Vasconcelos A. T., Ferreira H. B., Bizarro C. V., Bonatto S. L., Carvalho M. O., Pinto P. M., Almeida D. F., Almeida L. G., Almeida R. other authors 2005; Swine and poultry pathogens: the complete genome sequences of two strains of Mycoplasma hyopneumoniae and a strain of Mycoplasma synoviae . J Bacteriol 187:5568–5577
    [Google Scholar]
  79. Westberg J., Persson A., Holmberg A., Goesmann A., Lundeberg J., Johansson K. E., Pettersson B., Uhlen M. 2004; The genome sequence of Mycoplasma mycoides subsp. mycoides SC type strain PG1T, the causative agent of contagious bovine pleuropneumonia (CBPP. Genome Res 14:221–227
    [Google Scholar]
  80. Williams M. H., Brostoff J., Roitt I. M. 1970; Possible role of Mycoplasma fermentans in pathogenesis of rheumatoid arthritis. Lancet 2:277–280
    [Google Scholar]
  81. Wise K. S. 1993; Adaptive surface variation in mycoplasmas. Trends Microbiol 1:59–63
    [Google Scholar]
  82. Wise K. S., Kim M. F., Theiss P. M., Lo S. C. 1993; A family of strain-variant surface lipoproteins of Mycoplasma fermentans . Infect Immun 61:3327–3333
    [Google Scholar]
  83. Yavlovich A., Katzenell A., Tarshis M., Higazi A. A., Rottem S. 2004; Mycoplasma fermentans binds to and invades HeLa cells: involvement of plasminogen and urokinase. Infect Immun 72:5004–5011
    [Google Scholar]
  84. Zähringer U., Wagner F., Rietschel E. T., Ben-Menachem G., Deutsch J., Rottem S. 1997; Primary structure of a new phosphocholine-containing glycoglycerolipid of Mycoplasma fermentans . J Biol Chem 272:26262–26270
    [Google Scholar]
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