Chlamydia trachomatis is the leading bacterial agent of sexually transmitted infections in the United States and a major culprit in urethritis, cervicitis, endometritis, salpingitis, pelvic inflammatory disease, infertility and ectopic pregnancy. The highest chlamydial infection rates are observed in young people between 15 and 34 years of age. Throughout these peak reproductive years, the endometrial epithelial cell layer lining the uterine cavity is subject to constant changes in levels of micronutrients such as iron, due to hormonal cycling during menstruation. Endometrial epithelial cells are natural target host cells for infection by chlamydiae. The availability of iron is well-known to have a tremendous influence on the production of bacterial antigens, envelope components and virulence factors; these effects are particularly prominent for obligate intracellular pathogens such as chlamydiae. In other pathogens, virulence factors produced in response to low concentrations of iron elicit tissue damage in the host. Certain bacterial iron-regulated proteins are also immunotherapeutic targets for vaccine design. In these studies, the mechanism for regulation of chlamydial iron-responsive proteins and antigens will be examined in Specific Aim 1.
Specific Aims 2 and 3 will (i) determine the identities of chlamydial iron-regulated proteins, and (ii) quantitatively assess the transcription of the genes encoding these components under iron-deficient growth conditions, respectively.
In Specific Aim 4, an envelope transport system will be examined to determine whether or not it functions as a major iron-uptake pathway for the chlamydiae. The long-term objective for these studies are to develop a better understanding of mechanisms for the destructive tissue pathology observed in chlamydial infections and to provide new insights on specific chlamydial proteins and antigens that could be tested for their immunotherapeutic potential. ? ?
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