Chlamydial genital tract infections in women continue to be a huge public health problem in the United States and across the globe. These infections also can become personal tragedies for infected individuals since they frequently lead to upper genital tract sequelae that can result in involuntary infertility due to tubal scarring and occlusion. C. trachomatis genital tract infections in women also occur in a polymicrobial environment, but little information is available on how the female genital flora affects disease outcome caused by Chlamydiae. Recent studies demonstrate that C. trachomatis genital isolates differ from ocular strains in that the former have functional tryptophan biosynthetic genes, whereas ocular strains do not. Chlamydial strains that have the capacity to produce tryptophan may be at a distinct advantage in the in vivo environment, since a major chlamydial antimicrobial effect elicited by host immune reactivity is manifest in chlamydial host cells through the induction of a tryptophan decylcizing enzyme (indoleamine 2,3-dioxygenase, [IDO]) after activation by the CD4+, Th1 effector cytokine, gamma interferon. The tryptophan operon in genital C. trachomatis isolates, however, is incomplete in that indole or indole derivatives are required for tryptophan production by these strains. Indole is produced neither by Chlamydiae nor the human host, and the hypothesis to be tested in this application is that normal indole-producing genital flora contribute to Chlamydiae disease pathogenesis by producing the substrate necessary for C. trachomatis to survive and grow in the lower genital tract and thereby contribute to improved transmission potential as well as the possibility for more severe upper genital tract consequences. This hypothesis will be tested by determining the effects of indole-producing normal flora on chlamydial genital tract disease in a well-characterized murine model.
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