Patricia A.
Totten
PhD
Related Links
Research Interests
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.
Education & Training
PhD, Department of Microbiology & Immunology, University of Washington, Seattle WA, (1983-1990)
Postdoctoral Fellowship in Infectious Disease, Department of Medicine, University of Washington, Seattle WA, (1990-1995)
Honors
NIH/NIAID UO1 AI 31448: STD Cooperative Research Center Program Project Developmental Award (1991-1994)
ASHA/Burroughs Welcome Fund Postdoctoral Research Fellowship in Sexually Transmitted Diseases (1992-1994)
Peter Hannan Award for Outstanding Research in Applied Clinical Mycoplasmology (2010)
Publications
Burgos R and Totten PA. MG428 is a novel positive regulator of recombination that triggers mgpB and mgpC gene variation in Mycoplasma genitalium. Mol Microbiol. 2014; 94,290-306.
• PubMed Abstract
Wood GE, Iverson-Cabral SL, Patton DL, Cummings PK, Cosgrove Sweeney YT and Totten PAPersistence, immune response, and antigenic variation of Mycoplasma genitalium in an experimentally infected pig-tailed macaque (Macacca nemestrina). Infect. Immun. 2013; 812938-2951.
• PubMed Abstract
Burgos R, Wood GE, Young L, Glass JO, Totten PA. RecA mediates MgpB and MgpC phase and antigenic variation in Mycoplasma genitalium, but plays a minor role in DNA repair. Mol Microbiol. 2012; 85:669-683.
• PubMed Abstract
Cohen CR, Nosek M, Meier A, Astete AG, Iverson-Cabral SL, Mugo NR, Totten PA. Mycoplasma genitalium infection and persistence in a cohort of female sex workers in Nairobi, Kenya. Sex Transm Dis. 2007; 34:274-9.
• PubMed Abstract
Iverson-Cabral SL, Astete SG, Cohen CR, Rocha EPC, Totten PA. Intrastrain heterogeneity of the mgpB gene in Mycoplasma genitalium is extensive in vitro and in vivo and suggests that variation is generated via recombination with repetitive chromosomal sequences. Infect Immun. 2006; 74: 3715-26.
• PubMed Abstract
Manhar LE, Critchlow CW, Holmes KK, Dutro SM, Eschenbach DA, Stevens CE, Totten PA. Mucopurulent cervicitis and Mycoplasma genitalium. J Infect Dis. 2003; 187:650-7.
• PubMed Abstract
Totten PA, Schwartz MA, Sjostrom KE, et al. Association of Mycoplasma genitalium with nongonococcal urethritis in heterosexual men. J Infect Dis. 2001; 183:269-276.
• Oxford Journals Abstract