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Mycoplasma genitalium rapidly disseminates to the upper reproductive tracts and knees of female mice following vaginal inoculation.

ABSTRACT: Mycoplasma genitalium is an emerging sexually transmitted infection and in women is associated with notable reproductive tract syndromes such as cervicitis, pelvic inflammatory disease, and infertility. Investigations into the causal relationships of M. genitalium infections and clinical disease have been hindered largely by the lack of a well-established small-animal model of genital tract infection. To establish a murine model, female Swiss Webster mice were conditioned with either progesterone or estradiol and then inoculated intravaginally with M. genitalium type strain G37 or a contemporary Danish strain, M2300. Persistent lower tract infection was observed at up to 77 days postinoculation (d.p.i.). Upper reproductive tract colonization was observed as early as 3 d.p.i., with long-term infection observed in estradiol-treated (65%) and progesterone-treated (18%) animals. In the upper tract, more than 90% of M. genitalium PCR-positive samples were from the uterus and oviducts. Ultimately, gross hydrosalpinx was observed 21 days to 10 weeks p.i. in approximately 60% of infected animals, suggesting the presence of tubal occlusion. In addition, dissemination of M. genitalium to the knee tissues was observed as early as 7 d.p.i., with persistent infection detected at up to 28 d.p.i. Mice infected with M. genitalium also developed specific antibodies to the major antigenic outer membrane protein MgPa, elongation factor Tu, pyruvate dehydrogenase E1alpha, and DnaK (Hsp70), indicating persistent infection despite robust humoral responses to infection. These findings provide strong experimental evidence that M. genitalium can establish long-term infection of reproductive tract and joint tissues, with preliminary evidence of pathological reproductive tract outcomes.

SUBMITTER: McGowin CL

PROVIDER: S-EPMC2812211 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Mycoplasma genitalium rapidly disseminates to the upper reproductive tracts and knees of female mice following vaginal inoculation.

McGowin Chris L CL Spagnuolo Rae Ann RA Pyles Richard B RB

Infection and immunity 20091207 2

Mycoplasma genitalium is an emerging sexually transmitted infection and in women is associated with notable reproductive tract syndromes such as cervicitis, pelvic inflammatory disease, and infertility. Investigations into the causal relationships of M. genitalium infections and clinical disease have been hindered largely by the lack of a well-established small-animal model of genital tract infection. To establish a murine model, female Swiss Webster mice were conditioned with either progesteron ...[more]

PMID: 19995897

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Project description:Recent studies have suggested that the vaginal microenvironment plays a role in persistence of high-risk human papillomavirus (hrHPV) infection and thus cervical carcinogenesis. Furthermore, it has been shown that some mycoplasmas are efficient methylators and may facilitate carcinogenesis through methylation of hrHPV and cervical somatic cells. We examined associations between prevalence and persistence of Mycoplasma spp. in the vaginal microbiota, and prevalent as well as persistent hrHPV infections.We examined 194 Nigerian women who were tested for hrHPV infection using SPF25/LiPA10 and we identified Mycoplasma genitalium and Mycoplasma hominis in their vaginal microbiota established by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. We defined the prevalence of M. genitalium, M. hominis, and hrHPV based on positive result of baseline tests, while persistence was defined as positive results from two consecutive tests. We used exact logistic regression models to estimate associations between Mycoplasma spp. and hrHPV infections.The mean (SD) age of the study participants was 38 (8) years, 71% were HIV positive, 30% M. genitalium positive, 45% M. hominis positive, and 40% hrHPV positive at baseline. At follow-up, 16% of the women remained positive for M. genitalium, 30% for M. hominis, and 31% for hrHPV. There was a significant association between persistent M. hominis and persistent hrHPV (OR 8.78, 95% CI 1.49-51.6, p 0.01). Women who were positive for HIV and had persistent M. hominis had threefold increase in the odds of having persistent hrHPV infection (OR 3.28, 95% CI 1.31-8.74, p 0.008), compared to women who were negative for both.We found significant association between persistent M. hominis in the vaginal microbiota and persistent hrHPV in this study, but we could not rule out reverse causation. Our findings need to be replicated in larger, longitudinal studies and if confirmed, could have important diagnostic and therapeutic implications.

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Mycoplasma genitalium rapidly disseminates to the upper reproductive tracts and knees of female mice following vaginal inoculation.

Publications

Mycoplasma genitalium rapidly disseminates to the upper reproductive tracts and knees of female mice following vaginal inoculation.

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