It is proposed to examine critical new adaptive features of the multigene vlp (variable lipoprotein) system of Mycoplasma hyorhinis that were revealed during its initial molecular characterization in the past funding period. This system of variable surface lipoproteins (Vlps) is an instructive and well developed model for studying adaptive genetic strategies, and fundamental surface coat properties, of several wall-less mycoplasma species contributing to human and animal disease. The Vlp system produces non-coordinate, high frequency switching in the expression and in structural features of the major surface coat lipoproteins of M. hyorhinis, through intragenic mutations that independently affect transcription (Vlp phase variation), or the length of 3' repetitive coding regions (Vlp size variation) of divergent vlp genes clustered in the chromosome. Structural and combinatorial variation in Vlp profiles expressed on the unique single plasma membrane surface, may profoundly affect in-host adaptive capabilities of mycoplasmas, including their susceptibility to host Abs directed toward vital surface structures.
Specific aims will address important gaps in the understanding of this prototype system, including: (i) the range of variation in the natural repertoire of vlp genes, (ii) the degree, pattern and consequences of Vlp variation in an established model of M. hyorhinis-induced arthritis in the natural swine host, and (iii) the nature of host Ab interactions with Vlps and other surface proteins, including the possible role of Vlps in surface masking. Approaches include PCR-based characterization of vlp gene families in a series of primary isolates, assessment of Vlp profiles of organisms in situ or isolated from the animal host (by immunomicroscopy, PCR and immunochemical techniques), and analysis of Ab-mycoplasma interactions by similar methods. These efforts are expected to reveal important strategies of adaptive surface variation generally applicable to pathogenic mycoplasmas and to other microbes employing genetic variation as a survival strategy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI031656-07
Application #
2672085
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1991-08-01
Project End
2002-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
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Pincus, S H; Cole, R L; Watson-McKown, R et al. (1998) Immunologic cross-reaction between HIV type 1 p17 and Mycoplasma hyorhinis variable lipoprotein. AIDS Res Hum Retroviruses 14:419-25
Citti, C; Kim, M F; Wise, K S (1997) Elongated versions of Vlp surface lipoproteins protect Mycoplasma hyorhinis escape variants from growth-inhibiting host antibodies. Infect Immun 65:1773-85
Yogev, D; Watson-McKown, R; Rosengarten, R et al. (1995) Increased structural and combinatorial diversity in an extended family of genes encoding Vlp surface proteins of Mycoplasma hyorhinis. J Bacteriol 177:5636-43
Citti, C; Wise, K S (1995) Mycoplasma hyorhinis vlp gene transcription: critical role in phase variation and expression of surface lipoproteins. Mol Microbiol 18:649-60
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