PRIMATE MODEL FOR MYCOPLASMA GENITALIUM

University Of Washington, Seattle WA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In our grant, IR21AI074898, "A Primate Model of Mycoplasma genitalium" we are assessing the ability of pigtail macaques to serve as an animal model to study the immunopathogenesis of M. genitalium (MG), a newly recognized reproductive tract pathogen. In this model primates are inoculated cervically with MG then vaginal and cervical specimens are collected at intervals spanning 8 weeks for detection of MG by qPCR and culture. Biopsies are collected at Week 4 (Fallopian tube and fimbriae) and Week 8 (Fallopian tube, fimbriae and cervix) at which time the animals are treated to cure the MG infection. The biopsies are processed for culture, qPCR and histology to detect immune cell infiltration. Serum is collected prior to infection at and intervals to assess the production of anti-MG antibodies over the course of the infection. In the past year we have inoculated 4 of the 6 primates funded by this proposal with MG: 2 primates were successfully colonized throughout the 8 weeks of the study, one was colonized for 4-6 weeks and the fourth animal was not infected. Preliminary analysis of serum suggests that antibodies to MG are produced after infection that specifically recognized the immunodominant adhesin molecules, MgpB and MgpC. Culture and qPCR of the upper reproductive tract tissues suggests that MG has not ascended from the lower tract in these animals suggesting that longer experiments or repeated inoculations may be necessary to induce upper tract infection. Finally, experiments are underway to assess sequence variation in MgpB and MgpC during infection in response to antibody production. The final two primates funded by this grant are scheduled to undergo our protocol, scheduled for Feb-Aug 2011.