Salpingeal infection model of Mycoplasma genitalium

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DESCRIPTION (provided by applicant): Mycoplasma genitalium is a newly recognized cause of reproductive tract disease syndromes, including urethritis, mucopurulent cervicitis, pelvic inflammatory disease, and endometritis, with possible sequelae that include infertility, chronic pelvic pain, and preterm birth. Studies assessing the pathogenesis, immunobiology, and virulence factors of M. genitalium are currently being performed in several laboratories, yet are limited by the lack of an appropriate animal model. Chimpanzees, which are no longer available for experimental studies, have been previously used to demonstrate the ability of M. genitalium to cause disease and persist in the urethra, vagina, cervix, and oviducts of these animals. Although other primate species have been less extensively studied, M. genitalium has persistently infected, produced characteristic disease, and induced an antibody response in the majority of species tested. The availability of the Washington National Primate Research Center (WaNPRC) housed at the University of Washington, and the salpingeal pocket model developed by Dr. Patton, a co-investigator on this application, provides a unique opportunity to study the immunopathogenesis of M. genitalium infection. Dr. Totten's research demonstrating the disease associations of M. genitalium, the possible role of antigenic variation in the ability of this organism to persist in infected women, and her proven ability to culture this fastidious organism, provide the necessary expertise to study the molecular pathogenesis of this novel organism. We thus propose to assess the pigtailed macaque as an animal model to study the growth, persistence, and humoral antibody response to M. genitalium; determine the local immunobiology of disease; and evaluate the mechanisms used by M. genitalium to persist during infection. The salpingeal pocket model, developed by Dr. Patton and successfully employed for the elucidation of C. trachomatis infection, will be used to assess M. genitalium infection. The studies proposed herein will lead to future studies assessing the innate and adaptive host immune response to infection, the mechanisms used by M. genitalium to avoid the immune response and persist in vivo, the pathogenesis of M. genitalium infection, and the evaluation of microbicides to prevent infection. PUBLIC HEALTH RELEVANCE: Mycoplasma genitalium is a newly recognized sexually transmitted pathogen with a prevalence and significance that rivals that of Chlamydia trachomatis and Neisseria gonorrhoeae. Little is known about the mechanisms used by this bacterium to elicit disease, in part because suitable animal models have not been developed for this pathogen. Importantly, this organism has developed a potential mechanism of antigenic variation that may explain its ability to persist in infected individuals to cause chronic infections. We propose to develop a primate model to study the immunobiology of M. genitalium infection, using techniques that have been highly successful for the study of C. trachomatis. This model, developed at the Washington National Primate Research Center (WaNPRC), will provide a unique opportunity to study the host/bacterial interactions of M. genitalium in an animal and in tissues most closely related to human disease. Further, development of this model will provide future opportunity to assess strategies for prevention and treatment of this emerging pathogen.