Several genes involved in sterol synthesis have been cloned from C. glabrata. and C. albicans. The ERG3 gene, which encodes the 5,6 desaturase, has been cloned and sequenced from both species. The gene has been deleted from C. glabrata. The deletion has been confirmed by PRC, Southern and Northern analysis. The major sterol of this deletion mutant is fecosterol, which is consistent with a lack of desaturase activity. The deletion of this gene in C. glabrata does not, however, affect susceptibility to triazole antifungal agents. This differs from what has been observed in the closely related yeast S. cerevisiae and C. albicans, suggesting that the sterol requirement of C. glabrata differs from other related yeast. The C. glabrata ERG11 gene, encoding the cytochrome P-450-dependent x-14 demethylase, has been cloned and sequenced. Ura3 auxotrophic mutants in both the parent C. glabrata strain and it's erg3 deletion mutant were created by plating on 5-fluoro- orotic acid. Transformation with the S. cerevisiae URA3 gene revealed it to be functional in C. glabrata. A deletion construct using URA3 as a selectable marker has been made in order to disrupt this gene in C. glabrata and its' erg3 mutant. We have enrolled two patients in our clinical study: High Dose Fluconazole in the Treatment of Oropharyngeal Candidiasis Resistant to Low Dose Fluconazole. WE have no data to report at this time.
Showing the most recent 10 out of 29 publications
