THE IMPORTANCE OF PHENOTYPIC HETEROGENEITY IN MYCOPLASMAS

Abstract
Members of the genus Mycoplasma have several characteristic features, including small genome size in comparison to most other prokaryotes. The drastic reduction in their genome size during evolution was only possible by the adoption of a parasitic lifestyle, allowing these bacteria to acquire many nutrients from their hosts. As obligatory parasites, they were also forced to develop efficient strategies to avoid their hosts immune surveillance. A number of studies have demonstrated that mycoplasmas which colonize animals and humans are able to change their surface antigen profile at high frequency. Such antigenic variation is proposed to play a key role in the evasion from the host immune response. The mayor variable antigens at the mycoplasma cell surface are lipoproteins, which are also the dominant immunogens during mycoplasmal infections. These lipoprotein, depending upon the species, are encoded by single or multiple genes and undergo frequent phase and size variation during mycoplasma growth. A variety of genetic mechanisms are used to modulate the expression of these lipoprotein genes, including DNA rearrangements, nucleotide insertions and deletions gene conversions, and site specific recombination.

Key words
Mycoplasma, antigenic variation, LAMPs, specific recombination, diagnostic.

Bibliografía del artículo

1. Razin S. Peculiar properties of mycoplasmas: the smallest self-replicating prokaryotes. FEMS Microbiol. Lett 1992; 79:423-431.
2. Razin S., Yogev D., Naot Y. Molecular biology and pathogenicity of mycoplasmas. Microbiol Mol Biol Rev 1998; 62:1094-1156.
3. Rocha PCE., Blanchard A. Genomic repeats, genome plasticity and the dynamics of Mycoplasma evolution. Nucleic Acids Res 2002; 30:2031-2040.
4. Razin S. Comparative genomics of mycoplasmas. Wien Klin Wochenschr 1997; 109:551-556.
5. Fraser CM., Gocayne JD., White O., et al. The minimal gene complement of Mycoplasma genitalium. Science 1995; 270:397-403.
6. Himmelreich R., Hilbert H., Plagens H., et al. Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae. Nucleic Acids Res 1996; 24:4420-4449.
7. Fleischmann RD., Adams MD., White O., et al. Whole-genome random sequencing and assembly of Haemophilus influenzae. Rd. Science 1995; 269:496-512.
8. Himmelreich R., Plagens H., Hilbert H., et al. Comparative analysis of the genomes of the bacteria Mycoplasma pneumoniae and Mycoplasma genitalium. Nucl Acids Res 1997; 25:701-712.
9. Rosengarten R., Citti C., Glew M., et al. Host-pathogen interactions in mycoplasma pathogenesis: virulence and survival strategies of minimalist prokaryotes. Int J Med Microbiol 2000; 290:15-25.
10. Rosengarten R., Wise KS. Phenotypic switching in mycoplasmas: phase variation of diverse surface lipoproteins. Science 1990; 247:315-318.
11. Bhugra B., Voelker LL., Zou N., et al. Mechanism of antigenic variation in Mycoplasma pulmonis: interwoven, site-specific DNA inversions. Mol Microbiol 1995; 18:703-714.
12. Glew MD., Browning GF., Markham PF., et al. pMGA phenotypic variation in Mycoplasma gallisepticum ocurrs in vivo and is mediated by trinucleotide repeat length variation. Infect Immun 2000; 68:6027-6033.
13. Noormohammadi AH., Markham PF., Kanci A., et al. A novel mechanism for control of antigenic variation in the haemagglutinin gene family of Mycoplasma synoviae. Mol Microbiol 2000; 35:9119-9123.
14. Theiss P., Wise KS. Localized frameshift mutation generates selective, high-frequency phase variation of a surface lipoprotein encoded by a mycoplasma ABC transporter operon. J Bacteriol 1997; 179:4013-4022.
15. Henderson IR., Owen P., Nataro JP. Molecular switches the ON and OFF of bacterial phase variation. Mol Microbiol 1999; 33:919-932.
16. Rivera TJA., Cedillo RL., Vega BM. Micoplasmas y su importancia médica. Rev Biomed 2001; 12:262-271.
17. Horino A., Sasaki Y., Sasaki T., et al. Múltiple promoter inversions generate surface antigenic variation in Mycoplasma penetrans. J Bacteriol 2003; 158:231-242.
18. Neyrolles O., Chambaud I., Ferris S., et al. Phase variations of the Mycoplasma penetrans main surface lipoproteins increase diversity antigen. Infect Immun 1999; 67:1569-1578.
19. Theiss P., Kim MF., Wise KS. Differential protein expression and surface presentation generate high frequency antigenic variation in Mycoplasma fermentans. Infection Immun 1993; 61:5123-5128.
20. Dawson MS., Hayes MM., Wang RYH., et al. Detection and isolation of Mycoplasma fermentans from urine of HIV-1 infected patients. Arch Pathol Lab Med 1993; 117:511-514.
21. Lo SC., Tsai S., Benis JR., et al. Enhancement of HIV-1 cytocidal effects in CD+4 lymphocytes by the AIDS-associated Mycoplasmas. Nature 1991; 251:1074-1076.
22. Saillard C., Carle P., Bové JM., et al. Genetic and serologic relatedness between Mycoplasma fermentans strains and a mycoplasma recently identified in tissue of AIDS and non-AIDS patients. Res Virol 1990; 141:385-395.
23. Stadtlander CT., Zuhua C., Watson HL., et al. Protein and antigen heterogeneity among strains of Mycoplasma fermentans. Infect Immun 1991; 59:3319-3322.
24. Wise KS. Adaptive surface variation in mycoplasmas. Trends Microbiol 1993; 1:59-63.
25. Garcia M., Elfaki MG., Kleven SH. Analysis of the variability in expression of Mycoplasma gallisepticum surface antigens. Vet Microbiol 1994; 42:147-158.
26. Levisohn S., Rosengarten R., Yogev D. In vivo variation of Mycoplasma gallisepticum antigen expression in experimentally infected chickens. Vet Microbiol 1995; 45:219-231.
27. Rosengarten R., Yogev D. Variant colony surface antigenic phenotypes within mycoplasma strain populations: implications for species identification and strain standardization. J Clin Microbiol 1996; 34:149-158.
28. Roske K., Blanchard A., Chambaud I., et al. Phase variation among major surface antigens of Mycoplasma penetrans. Infect Immun 2001; 69:7642-7651