Research in the Totten group focuses on the discovery, epidemiology, and molecular pathogenesis of novel bacteria associated with idiopathic reproductive tract diseases in men and women. For example, in collaborative studies with clinicians and epidemiologists, we have shown that Mycoplasma genitalium and Ureaplasma urealyticum, two newly recognized bacterial species, are associated with urethritis in men from whom no known pathogens were identified. Significantly, we have also shown that Mycoplasma genitalium is associated with cervicitis, endometritis, pelvic inflammatory disease, HIV shedding, and preterm birth. Our studies have also demonstrated that this organism can persist for months, if not years, in infected women and as a result we have proposed that antigenic variation within surface-exposed proteins in its unique and complex attachment organelle contributes to this persistence. Supporting this hypothesis, we demonstrated that the genes encoding these proteins are extremely heterogeneous in vivo and in vitro and vary by reciprocal recombination with archived DNA sequences on its minimal chromosome. The identification and regulation of recombination genes required for this variation, the effect of gene variation on the antigenicity of the resulting proteins, and the role of antigenic variation on immune evasion, and the development of a primate model for infection n are ongoing studies in the Totten laboratory.
Totten, P.A., Schwartz, M.A., Sjostrom, K.E., Kenny, G.E., Handsfield, H.H., Weiss, J.B., & Whittington, W.L.H. (2001). Association of Mycoplasma genitalium with nongonococcal urethritis in heterosexual men. J Infect Dis, 183, 269-276. PMID: 11120932.
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Oxford Journals Abstract ]
Manhart, L.E., Critchlow, C.W., Holmes, K.K., Dutro, S.M., Eschenbach, D.A., Stevens, C.E., & Totten, P.A. (2003). Mucopurulent cervicitis and Mycoplasma genitalium. J Infect Dis, 187, 650-657.
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PubMed
Abstract ]
Iverson-Cabral, S.L., Astete, S.G., Cohen, C.R., Rocha, E.P.C., & Totten, P.A. (2006). 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, 74, 3715-3726.
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PubMed
Abstract ]
Cohen, C.R., Nosek, M., Meier, A., Astete, A. G., Iverson-Cabral, S.L., Mugo, N.R., & Totten, P.A. (2007). Mycoplasma genitalium infection and persistence in a cohort of female sex workers in Nairobi, Kenya. Sex Transm Dis, 34, 274-279
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PubMed
Abstract ]
Iverson-Cabra,S.L., Astete, S. G., Cohen, C.R., & Totten, P.A. (2007). mgpB and mgpC sequence diversity in Mycoplasma genitalium is generated by segmental reciprocal recombination with repetitive chromosomal sequences. Mol Microbiol, 66, 56-75.
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PubMed
Abstract ]
Ondondo, R.O., Whittington, W.L.H., Astete, S.G., & Totten, P.A. (2010). Differential association of ureaplasma species with nongonococcal urethritis in heterosexual men. Sex Trans Infect, 86, 271-275. PMID: 20460265
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STI
Abstract ]
Burgos, R., Wood, G.E., Young, L., Glass, J.O., & Totten, P.A. (2012). RecA mediates MgpB and MgpC phase and antigenic variation in Mycoplasma genitalium, but plays a minor role in DNA repair. Mol Microbiol, 85, 669-683. PMID: 2268642
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