We report on the first cloning and nucleotide sequencing of an ERG11 allele from a clinical isolate of Candida kefyr cross-resistant to azole antifungals. It was recovered from a stem cell transplant patient, in an oncohematology unit exhibiting unexpected high prevalence of C. kefyr. Two amino acid substitutions were identified: K151E, whose role in fluconazole resistance was already demonstra...

Hsp90 is a molecular chaperone that governs drug resistance, morphogenesis, and virulence in the leading human fungal pathogen Candida albicans. Previous work with Saccharomyces cerevisiae and C. albicans established acetylation as a novel mechanism of post-translational control of Hsp90 in fungi and implicated lysine deacetylases (KDACs) as key regulators of resistance to the most common class...

The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole su...

OBJECTIVES To determine the mechanisms responsible for fluconazole resistance in two Candida albicans isolates (CAAL2 and CAAL76) recovered from two hospitalized patients after fluconazole prophylaxis. METHODS MICs of fluconazole and voriconazole were determined by the broth microdilution method (CLSI M27-A3), and by Etest(®) for amphotericin B. RNA expression levels of CDR1, MDR1 and ERG11 w...

Antifungal resistance and virulence properties of Candida albicans are a growing health problem worldwide. To study the expression of virulence and azole resistance genes in 39 clinical strains of C. albicans, we used a model of infection of human vaginal epithelial cells with C. albicans strains isolated from Mexican women with vulvovaginal candidiasis (VVC). The strains were identified by PCR...

OBJECTIVES To determine the MIC distributions of itraconazole, voriconazole and posaconazole and non-azole drugs for wild-type cyp51A, as well as TR(34)/L98H and TR(46)/Y121F/T289A cyp51A mutants of Aspergillus fumigatus. METHODS We retrieved MIC and cyp51A sequence data for 952 clinical A. fumigatus strains isolated in or referred to our reference laboratory, during the January 2010 to Decem...

The evolution of drug resistance in fungal pathogens compromises the efficacy of the limited number of antifungal drugs. Drug combinations have emerged as a powerful strategy to enhance antifungal efficacy and abrogate drug resistance, but the impact on the evolution of drug resistance remains largely unexplored. Targeting the molecular chaperone Hsp90 or its downstream effector, the protein ph...

Patients with hematologic malignancies as well as allogeneic hematopoietic stem cell transplantation (HSCT) patients are at high risk for invasive aspergillosis. Here, we report a culture- and autopsy-proven fatal invasive aspergillosis in an allogeneic HSTC patient which he developed despite posaconazole prophylaxis. The agent was determined to be an azole-resistant Aspergillus fumigatus strai...

conclusions the findings show fluconazole -resistance in c. albicans isolates with overexpression of pir1p. results in the 52 isolates, 49 (94%) were resistant to fluconazole. overexpression of pir1 gene was detected in 47 (96%) fluconazole-resistant c. albicans isolates. patients and methods a total of 52l vaginal samples were obtained from the females with c. albicans vaginitis. the azole sus...

OBJECTIVES Triazole resistance in Aspergillus fumigatus has been increasing. We explored the A. fumigatus azole resistance profiles in bronchoalveolar lavage (BAL) fluid samples from Danish patients examined for aspergillosis. METHODS A total of 94 BAL samples from 87 patients were evaluated by galactomannan (GM) test and A. fumigatus CYP51A profiling by PCR. RESULTS Aspergillus spp. were i...