| Vaginal candidiasis affects approximately 75% of all women. Candida albicans is the etiological agent in over 80% of vaginal candidiasis cases. Attributes of both C. albicans and the host contribute to development of vaginal candidiasis. The studies presented in this dissertation used two different experimental approaches to assess the effect of the host vaginal environment on the cellular and molecular biology of C. albicans. The first approach evaluated the expression of the eight agglutinin-like sequence (ALS) genes in clinical vaginal specimens and in models of vaginal candidiasis, including a murine model and an in vitro tissue model. The ALS genes encode large cell-surface glycoproteins that are candidates for aiding C. albicans colonization of the vaginal epithelium and/or for promoting development of vaginal disease. Vaginal-specific patterns of ALS gene expression were detected using reverse transcription-PCR and suggested that ALS gene expression is specific to the host site where C. albicans cells are located. The second experimental approach was prompted by reports in the scientific literature that suggested a positive association between elevated estrogen concentration and the incidence of vaginal candidiasis. The goal of this study was to determine the effect of estrogen on the growth characteristics and transcriptional profile of C. albicans cultured in defined media. Addition of estrogen to C. albicans cells resulted in increased germ tube formation and length in an estrogen-, dose- and strain-dependent manner, but did not have a significant effect on culture biomass. Genes that were differentially expressed in the presence of estrogen were defined by microarray analysis and included CDR1 and CDR2. Analysis of estrogen-exposed strain DSY654, that lacks CDR1 and CDR2 coding sequences, showed a significantly decreased number of germ tube-forming cells in the presence of estrogen. PDR16 was the most highly up-regulated gene in strain DSY654 under the growth conditions assayed. The cell biology and gene expression data led to a model to explain how components of the phospholipid and sterol metabolic pathways may interact to affect C. albicans germ tube formation and length. Collectively these two different experimental approaches produced new insight into the interaction between C. albicans and the vaginal environment. |
