- Adjunct Research Professor, Global Health
- Research Professor, Medicine - Allergy and Infectious Dis.
Harborview Medical Center
R & T Building
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Research in the Totten group focuses on the molecular biology, pathogenesis, and disease associations of the recently discovered STD pathogen, Mycoplasma genitalium. Their finding that this bacterium can persist 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, they have shown that the sequences of the genes encoding these proteins evolve using 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, they have shown that recombination leading to antigenic variation is regulated at the transcriptional, 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 in our experimental primate model are ongoing studies in the Totten laboratory. The significance of these findings is emphasized by our other ongoing studies, performed in collaboration with epidemiologists and clinicians, linking M. genitalium with STD syndromes and their sequelae, developing new diagnostics, and defining effective treatment regimens for this increasingly antibiotic-resistant bacterium.
- Host-pathogen Interactions
- Infectious Diseases
- STDs (other than HIV)
Wood GE, SL Iverson-Cabral, DL Patton, PK Cummings, YT Cosgrove Sweeney, and PA Totten. Experimental infection of pigtailed macaques (Macaca nemestrina) with Mycoplasma genitalium. 2017. Inf. Immun.85:00338-16.
Iverson-Cabral SL, GE Wood, PA Totten. 2015. Analysis of the Mycoplasma genitalium MgpB adhesion to predict membrane topology, investigate antibody accessibility, characterize amino acid diversity, and identify functional and immunogenic epitopes. PLOS One, PMC4575044
Burgos R and Totten PA. 2014. MG428 is a novel positive regulator of recombination that triggers mgpB and mgpC gene variation in Mycoplasma genitalium. Mol. Microbiol. 94:290-306.PMCID: PMC4203370.
Burgos R and PA Totten. 2014. Characterization of the operon encoding the Holliday junction helicase RuvAB from Mycoplasma genitalium and its role in mgpB and mgpC gene variation. J. Bacteriol 196:1608-1618. PMID: 24532771. PMC 3993354
Manhart, LE, CW Gillespie, MS Lowens, CM Khosropour, DV Colombara, MR Golden, NR Hakhu, KK Thomas, JP Hughes, NL Jensen, and PA Totten. 2013. Standard treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized controlled trial. Clin. Infect. Dis. 56: 934-942. PMID 23223595. PMC3588116