Azole antifungal agents such as fluconazole exhibit fungistatic activity against Candida albicans. Strategies to enhance azole antifungal activity would be therapeutically appealing. In an effort to identify transcriptional pathways that influence the killing activity of fluconazole, we sought to identify transcription factors (TFs) involved in this process. From a collection of C. albicans str...

Histatins are a group of small, cationic, antifungal peptides present in human saliva. A previous molecular modeling analysis suggested structural similarity between the Phe14-His15 and His18-His19 dipeptide sequences in histatin-5 (Hsn-5; a 24-amino-acid polypeptide) and the sequence of miconazole (one of the azole-based antifungal therapeutic agents), implying that the mechanisms of killing o...

Pdr5p-like ABC transporters play a significant role in azole resistance in Saccharomyces cerevisiae and Candida spp. Most of filamentous fungal species have multiple Pdr5p homologues. In this study, phylogenic analysis identified that filamentous fungi have at least two phylogenically distant groups of Pdr5p homologues. One contains PMR1-like Pdr5p homologues while the other contains both AtrF-...

Case report-Subjects-Three cases are described oflong-standing vaginal candidosis due to Candida glabrata. These had failed to respond to local and systemic antifungals. In each case the infecting strain appeared resistant to a range of azole drugs in vitro. Clinical course-Case one-This patient recovered following prolonged treatment with oral itraconazole in combination with oral and vaginal ...

Candida spp. are common causes of bloodstream infections among hospitalized patients. Fluconazole (FLC) remains a first-line therapy for candidemia; and voriconazole (VRC), an expanded-spectrum triazole, was recently approved for the treatment of candidemia in nonneutropenic patients. In vitro studies have suggested that VRC has potent activity against Candida spp. with reduced susceptibilities...

Candida albicans biofilms are formed through three distinct developmental phases and are associated with high fluconazole (FLU) resistance. In the present study, we used a set of isogenic Candida strains lacking one or more of the drug efflux pumps Cdr1p, Cdr2p, and Mdr1p to determine their role in FLU resistance of biofilms. Additionally, variation in sterol profile as a possible mechanism of ...

Saccharomyces cerevisiae has long been used as a model organism in the study of the ergosterol pathway and its inhibitors. The Pdr5 protein (Pdr5p), an ATP binding cassette transporter, plays an important role in active efflux of azole antifungals and therefore in azole sensitivity and resistance in S. cerevisiae. We have identified the Fluconazole Dominant Resistance-1 (FDR-1) mutant, which ha...

Molecular studies have shown that the majority of azole resistance in Aspergillus fumigatus is associated with amino acid substitutions in the cyp51A gene. To obtain insight into azole resistance mutations, the cyp51A gene of 130 resistant and 76 susceptible A. fumigatus isolates was sequenced. Out of 130 azole-resistant isolates, 105 contained a tandem repeat of 34 bp in the promoter region an...