Candida albicans: The estrogen target for vaginal colonization

Background. Estradiol (E₂) stimulates colonization of the vagina by Candida albicans. Although this yeast expresses an estrogen-binding protein (EBP), the cellular target for estrogenic modulation of this infection is unresolved. Findings support direct E₂-induced C. albicans growth as well as indirect effects via E₂-induced changes in the vaginal epithelium. Our primary goal was to pursue the issue of direct versus indirect estrogen action on vaginal candidiasis using diethylstilbestrol (DES), an efficacious mammalian estrogen receptor agonist, which exhibits no detectable affinity for the EBP of C. albicans. Methods. We used both in vitro and in vivo experimentation with an EBP-positive strain of C. albicans isolated from the human vagina. Ligand-binding studies were performed with steroidal and nonsteroidal estrogens and anti-estrogens using the soluble EBP from both the yeast and the rat uterus. Mature ovariectomized rats were treated with either E₂ or DES for 7 days before and after C. albicans inoculation into the vaginas. Subsequent estrogen-sensitive colonization was quantified based on cultures of vaginal homogenates on Sabouraud dextrose (SD) agar pour plates. Results. We confirmed that our isolate of C. albicans contained a high-affinity EBP, with no detectable affinity for DES. Vaginal colonization by C. albicans was 8.6-fold greater in response to in vivo treatment with E₂ than with the comparable dose regimen of DES. Conclusions. The mechanism for estrogen-sensitive vaginal colonization by C. albicans includes a functional ligand-EBP interaction within the yeast.