MOLECULAR GENETIC BASIS OF MYCOPLASMA ANTIGEN VARIATION

点击翻译按钮获取中文摘要

DESCRIPTION (Adapted from the applicant's abstract): 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.