POLYMORPHIC MEMBRANE PROTEINS OF CHLAMYDIA TRACHOMATIS

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DESCRIPTION (provided by applicant): Chlamydial polymorphic membrane proteins (Pmps) are a newly identified family of Chlamydia-specific membrane proteins, whose role in chlamydial biology and pathogenesis is unknown. Genomic analysis of the pmp family of C. pneumoniae have revealed frameshift mutations, deletions and gene duplications. Studies of the larger pmp families of C. pneumoniae and C. psittaci have also revealed that Pmp proteins are expressed in vitro, that some can be detected at the elementary body surface, and that some are dominant antigens during infection and may be targets for vaccine design. The emerging evidence is consistent with a role of the pmp family in pathogenesis and immune evasion. The purpose of this project is to characterize the smallest pmp family identified to date: the 9-member pmp family of C. trachomatis. In preliminary studies using the 9 partially purified recombinant Pmps as target antigens, we have observed differential Pmp-specific antibody responses in archived sera from patients with pelvic inflammatory disease. This analysis will be expanded through cross-sectional and longitudinal comparisons of Pmp-specific responses in a well-characterized patient population with genital C. trachomatis l infection. This analysis may identify direct relationships between Pmp-specific responses and disease outcome. More importantly, this analysis will provide a set of fresh clinical C. trachomatis isolates for further I molecular characterization. A second focus of this project will be to identify and characterize determinants of pmp expression in C. trachomatis. Polymorphisms will be identified and compared in the pmp families of selected study isolates. Experiments will be performed to characterize developmental patterns of pmp expression in these isolates. Using a panel of Pmp-specific monoclonal and polyclonal antibodies generated in this project, we will examine Pmp protein expression and eventual translocation to the surface of the outer membrane along development and at the single cell level using laser scanning confocal fluorescence microscopy.