Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Jul;64(7):2737–2744. doi: 10.1128/iai.64.7.2737-2744.1996

Molecular basis of size and antigenic variation of a Mycoplasma hominis adhesin encoded by divergent vaa genes.

Q Zhang 1, K S Wise 1
PMCID: PMC174134  PMID: 8698503

Abstract

The molecular basis for the size and antigenic diversity of the variable adherence-associated (Vaa) antigen, a major surface protein and a putative adhesin (of Mycoplasma hominis, is described. Size-variant alleles of the single-copy vaa gene encode abundant surface lipoproteins containing one to four nearly identical, tandem repetitive units of 121 amino acids in the central region of the mature Vaa product. Gain or loss of central repeats in vaa genes gives rise to distinct size-variant Vaa antigens in clonal populations of this organism. The N-terminal and repeat regions of Vaa contain highly conserved sequences, while the C-terminal region, implicated as the adherence-mediating module, is highly variable and divergent among different strains of this pathogen. Sequence variation in this region may underlie the strain-dependent binding of some monoclonal antibodies to Vaa products. The Vaa antigen is expressed in vivo during chronic, active arthritis associated with M. hominis infection and is highly immunogenic in the human host. Size variation and C-terminal antigenic divergence of Vaa could affect the adherence of M. hominis and evasion of antibody-mediated immunity, thereby contributing to the organism's adaptive capability in the human host. Variation in vaa genes reveals a distinct pattern of mutations generating mycoplasma surface variation.

Full Text

The Full Text of this article is available as a PDF (541.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barile M. F., Kapatais-Zoumbos K., Snoy P., Grabowski M. W., Sneller M., Miller L., Chandler D. K. Experimentally induced septic arthritis in chimpanzees infected with Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum. Clin Infect Dis. 1994 May;18(5):694–703. doi: 10.1093/clinids/18.5.694. [DOI] [PubMed] [Google Scholar]
  2. Bhugra B., Voelker L. L., Zou N., Yu H., Dybvig K. Mechanism of antigenic variation in Mycoplasma pulmonis: interwoven, site-specific DNA inversions. Mol Microbiol. 1995 Nov;18(4):703–714. doi: 10.1111/j.1365-2958.1995.mmi_18040703.x. [DOI] [PubMed] [Google Scholar]
  3. Christiansen G., Mathiesen S. L., Nyvold C., Birkelund S. Analysis of a Mycoplasma hominis membrane protein, P120. FEMS Microbiol Lett. 1994 Aug 1;121(1):121–127. doi: 10.1111/j.1574-6968.1994.tb07085.x. [DOI] [PubMed] [Google Scholar]
  4. Citti C., Wise K. S. Mycoplasma hyorhinis vlp gene transcription: critical role in phase variation and expression of surface lipoproteins. Mol Microbiol. 1995 Nov;18(4):649–660. doi: 10.1111/j.1365-2958.1995.mmi_18040649.x. [DOI] [PubMed] [Google Scholar]
  5. Cleavinger C. M., Kim M. F., Im J. H., Wise K. S. Identification of mycoplasma membrane proteins by systematic Tn phoA mutagenesis of a recombinant library. Mol Microbiol. 1995 Oct;18(2):283–293. doi: 10.1111/j.1365-2958.1995.mmi_18020283.x. [DOI] [PubMed] [Google Scholar]
  6. Dallo S. F., Baseman J. B. Adhesin gene of Mycoplasma genitalium exists as multiple copies. Microb Pathog. 1991 Jun;10(6):475–480. doi: 10.1016/0882-4010(91)90113-o. [DOI] [PubMed] [Google Scholar]
  7. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dramsi S., Dehoux P., Cossart P. Common features of gram-positive bacterial proteins involved in cell recognition. Mol Microbiol. 1993 Sep;9(5):1119–1121. doi: 10.1111/j.1365-2958.1993.tb01241.x. [DOI] [PubMed] [Google Scholar]
  9. Dybvig K. DNA rearrangements and phenotypic switching in prokaryotes. Mol Microbiol. 1993 Nov;10(3):465–471. doi: 10.1111/j.1365-2958.1993.tb00919.x. [DOI] [PubMed] [Google Scholar]
  10. Emanuel J. R. Simple and efficient system for synthesis of non-radioactive nucleic acid hybridization probes using PCR. Nucleic Acids Res. 1991 May 25;19(10):2790–2790. doi: 10.1093/nar/19.10.2790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fischetti V. A. Streptococcal M protein. Sci Am. 1991 Jun;264(6):58–65. doi: 10.1038/scientificamerican0691-58. [DOI] [PubMed] [Google Scholar]
  12. 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., Kelley J. M. The minimal gene complement of Mycoplasma genitalium. Science. 1995 Oct 20;270(5235):397–403. doi: 10.1126/science.270.5235.397. [DOI] [PubMed] [Google Scholar]
  13. Henrich B., Feldmann R. C., Hadding U. Cytoadhesins of Mycoplasma hominis. Infect Immun. 1993 Jul;61(7):2945–2951. doi: 10.1128/iai.61.7.2945-2951.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hollingshead S. K., Fischetti V. A., Scott J. R. Size variation in group A streptococcal M protein is generated by homologous recombination between intragenic repeats. Mol Gen Genet. 1987 May;207(2-3):196–203. doi: 10.1007/BF00331578. [DOI] [PubMed] [Google Scholar]
  15. Kawula T. H., Spinola S. M., Klapper D. G., Cannon J. G. Localization of a conserved epitope and an azurin-like domain in the H.8 protein of pathogenic Neisseria. Mol Microbiol. 1987 Sep;1(2):179–185. doi: 10.1111/j.1365-2958.1987.tb00510.x. [DOI] [PubMed] [Google Scholar]
  16. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  17. Ladefoged S. A., Birkelund S., Hauge S., Brock B., Jensen L. T., Christiansen G. A 135-kilodalton surface antigen of Mycoplasma hominis PG21 contains multiple directly repeated sequences. Infect Immun. 1995 Jan;63(1):212–223. doi: 10.1128/iai.63.1.212-223.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Levinson G., Gutman G. A. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol Biol Evol. 1987 May;4(3):203–221. doi: 10.1093/oxfordjournals.molbev.a040442. [DOI] [PubMed] [Google Scholar]
  20. Lucier T. S., Hu P. Q., Peterson S. N., Song X. Y., Miller L., Heitzman K., Bott K. F., Hutchison C. A., 3rd, Hu P. C. Construction of an ordered genomic library of Mycoplasma genitalium. Gene. 1994 Dec 2;150(1):27–34. doi: 10.1016/0378-1119(94)90853-2. [DOI] [PubMed] [Google Scholar]
  21. Markham P. F., Glew M. D., Sykes J. E., Bowden T. R., Pollocks T. D., Browning G. F., Whithear K. G., Walker I. D. The organisation of the multigene family which encodes the major cell surface protein, pMGA, of Mycoplasma gallisepticum. FEBS Lett. 1994 Oct 3;352(3):347–352. doi: 10.1016/0014-5793(94)00991-0. [DOI] [PubMed] [Google Scholar]
  22. Markham P. F., Glew M. D., Whithear K. G., Walker I. D. Molecular cloning of a member of the gene family that encodes pMGA, a hemagglutinin of Mycoplasma gallisepticum. Infect Immun. 1993 Mar;61(3):903–909. doi: 10.1128/iai.61.3.903-909.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Neimark H. C. Division of mycoplasmas into subgroups. J Gen Microbiol. 1970 Oct;63(2):249–263. doi: 10.1099/00221287-63-2-249. [DOI] [PubMed] [Google Scholar]
  24. Olson L. D., Gilbert A. A. Characteristics of Mycoplasma hominis adhesion. J Bacteriol. 1993 May;175(10):3224–3227. doi: 10.1128/jb.175.10.3224-3227.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Olson L. D., Renshaw C. A., Shane S. W., Barile M. F. Successive synovial Mycoplasma hominis isolates exhibit apparent antigenic variation. Infect Immun. 1991 Sep;59(9):3327–3329. doi: 10.1128/iai.59.9.3327-3329.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Olson L. D., Shane S. W., Karpas A. A., Cunningham T. M., Probst P. S., Barile M. F. Monoclonal antibodies to surface antigens of a pathogenic Mycoplasma hominis strain. Infect Immun. 1991 May;59(5):1683–1689. doi: 10.1128/iai.59.5.1683-1689.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Robertson B. D., Meyer T. F. Genetic variation in pathogenic bacteria. Trends Genet. 1992 Dec;8(12):422–427. doi: 10.1016/0168-9525(92)90325-x. [DOI] [PubMed] [Google Scholar]
  28. Rosengarten R., Wise K. S. Phenotypic switching in mycoplasmas: phase variation of diverse surface lipoproteins. Science. 1990 Jan 19;247(4940):315–318. doi: 10.1126/science.1688663. [DOI] [PubMed] [Google Scholar]
  29. Rosengarten R., Wise K. S. The Vlp system of Mycoplasma hyorhinis: combinatorial expression of distinct size variant lipoproteins generating high-frequency surface antigenic variation. J Bacteriol. 1991 Aug;173(15):4782–4793. doi: 10.1128/jb.173.15.4782-4793.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Simmons W. L., Zuhua C., Glass J. I., Simecka J. W., Cassell G. H., Watson H. L. Sequence analysis of the chromosomal region around and within the V-1-encoding gene of Mycoplasma pulmonis: evidence for DNA inversion as a mechanism for V-1 variation. Infect Immun. 1996 Feb;64(2):472–479. doi: 10.1128/iai.64.2.472-479.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Smith G. P. Evolution of repeated DNA sequences by unequal crossover. Science. 1976 Feb 13;191(4227):528–535. doi: 10.1126/science.1251186. [DOI] [PubMed] [Google Scholar]
  32. Sneller M., Wellborne F., Barile M. F., Plotz P. Prosthetic joint infection with Mycoplasma hominis. J Infect Dis. 1986 Jan;153(1):174–175. doi: 10.1093/infdis/153.1.174. [DOI] [PubMed] [Google Scholar]
  33. Su C. J., Chavoya A., Baseman J. B. Regions of Mycoplasma pneumoniae cytadhesin P1 structural gene exist as multiple copies. Infect Immun. 1988 Dec;56(12):3157–3161. doi: 10.1128/iai.56.12.3157-3161.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sutcliffe I. C., Russell R. R. Lipoproteins of gram-positive bacteria. J Bacteriol. 1995 Mar;177(5):1123–1128. doi: 10.1128/jb.177.5.1123-1128.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Talay S. R., Valentin-Weigand P., Timmis K. N., Chhatwal G. S. Domain structure and conserved epitopes of Sfb protein, the fibronectin-binding adhesin of Streptococcus pyogenes. Mol Microbiol. 1994 Aug;13(3):531–539. doi: 10.1111/j.1365-2958.1994.tb00448.x. [DOI] [PubMed] [Google Scholar]
  36. Theiss P. M., Kim M. F., Wise K. S. Differential protein expression and surface presentation generate high-frequency antigenic variation in Mycoplasma fermentans. Infect Immun. 1993 Dec;61(12):5123–5128. doi: 10.1128/iai.61.12.5123-5128.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Theiss P., Karpas A., Wise K. S. Antigenic topology of the P29 surface lipoprotein of Mycoplasma fermentans: differential display of epitopes results in high-frequency phase variation. Infect Immun. 1996 May;64(5):1800–1809. doi: 10.1128/iai.64.5.1800-1809.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Weisburg W. G., Tully J. G., Rose D. L., Petzel J. P., Oyaizu H., Yang D., Mandelco L., Sechrest J., Lawrence T. G., Van Etten J. A phylogenetic analysis of the mycoplasmas: basis for their classification. J Bacteriol. 1989 Dec;171(12):6455–6467. doi: 10.1128/jb.171.12.6455-6467.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Welch R. A. Pore-forming cytolysins of gram-negative bacteria. Mol Microbiol. 1991 Mar;5(3):521–528. doi: 10.1111/j.1365-2958.1991.tb00723.x. [DOI] [PubMed] [Google Scholar]
  40. Wise K. S. Adaptive surface variation in mycoplasmas. Trends Microbiol. 1993 May;1(2):59–63. doi: 10.1016/0966-842X(93)90034-O. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wise K. S., Watson R. K. Mycoplasma hyorhinis GDL surface protein antigen p120 defined by monoclonal antibody. Infect Immun. 1983 Sep;41(3):1332–1339. doi: 10.1128/iai.41.3.1332-1339.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wren B. W. A family of clostridial and streptococcal ligand-binding proteins with conserved C-terminal repeat sequences. Mol Microbiol. 1991 Apr;5(4):797–803. doi: 10.1111/j.1365-2958.1991.tb00752.x. [DOI] [PubMed] [Google Scholar]
  43. Yamao F., Muto A., Kawauchi Y., Iwami M., Iwagami S., Azumi Y., Osawa S. UGA is read as tryptophan in Mycoplasma capricolum. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2306–2309. doi: 10.1073/pnas.82.8.2306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yogev D., Rosengarten R., Watson-McKown R., Wise K. S. Molecular basis of Mycoplasma surface antigenic variation: a novel set of divergent genes undergo spontaneous mutation of periodic coding regions and 5' regulatory sequences. EMBO J. 1991 Dec;10(13):4069–4079. doi: 10.1002/j.1460-2075.1991.tb04983.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Yogev D., Watson-McKown R., Rosengarten R., Im J., Wise K. S. Increased structural and combinatorial diversity in an extended family of genes encoding Vlp surface proteins of Mycoplasma hyorhinis. J Bacteriol. 1995 Oct;177(19):5636–5643. doi: 10.1128/jb.177.19.5636-5643.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Zheng X., Teng L. J., Watson H. L., Glass J. I., Blanchard A., Cassell G. H. Small repeating units within the Ureaplasma urealyticum MB antigen gene encode serovar specificity and are associated with antigen size variation. Infect Immun. 1995 Mar;63(3):891–898. doi: 10.1128/iai.63.3.891-898.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES