Patricia A. Totten, PhD

Research in the Totten group focuses on the molecular biology and pathogenesis of the recently discovered STD pathogen, Mycoplasma genitalium. How this organism survives in vivo despite its extremely reduced genome, the smallest of any free-living cellular form of life, is one of the research areas being studied by our group. Our finding that M. genitalium can persists for months, if not years, in infected women lead to our hypothesis that this pathogen evades the host immune response, in part, by antigenically varying two of its immunogenic surface-exposed proteins. Supporting this hypothesis, we have shown that the sequences of the genes encoding these proteins evolve in vivo using a unique mechanism of reciprocal recombination with non-coding homologous DNA distributed throughout its minimal chromosome.

Further, contrary to the accepted wisdom that this bacterium contains few regulatory genes, we have shown that recombination leading to antigenic variation is regulated at the transcriptio nal, post transcriptional, and translational levels. The novel recombination and regulatory mechanisms of antigenic variation, the biologic significance of the resulting antigenic variants, and the immunopathology of M. genitalium infection in human and in experimental primate model are ongoing studies in the Totten laboratory. In addition to the studies outlined above, we have worked closely with epidemiologists and clinicians to define the disease associations of M. genitalium, which include urethritis in men and cervicitis, acute endometritis, and chronic pelvic inflammatory disease as well as cervical shedding of HIV.

The results of our recently completed treatment trial revealed that antimicrobial resistance of M. genitalium is correlated with clinical failure and persistence of this organism in vivo. Further, these studies have provided us with recent (and numerous) isolates of this pathogen with matched serum specimens and clinical correlates, providing a link between our basic science and translation studies.