TAC1 (for transcriptional activator of CDR genes) is critical for the upregulation of the ABC transporters CDR1 and CDR2, which mediate azole resistance in Candida albicans. While a wild-type TAC1 allele drives high expression of CDR1/2 in response to inducers, we showed previously that TAC1 can be hyperactive by a gain-of-function (GOF) point mutation responsible for constitutive high expressi...

Azole resistance in Aspergillus fumigatus has emerged as a global health problem. Although the number of cases of azole-resistant aspergillosis is still limited, resistance mechanisms continue to emerge, thereby threatening the role of the azole class in the management of diseases caused by Aspergillus. The majority of cases of azole-resistant disease are due to resistant A. fumigatus originati...

The prevalence of invasive aspergillosis (IA) at the intensive care unit (ICU) is unknown and difficult to assess since IA also develops in patients lacking specific host factors. In the Netherlands, increasing azole-resistance in Aspergillus fumigatus complicates treatment of patients with IA. The aim of this study was to determine the prevalence of IA by azole-resistant A. fumigatus at the IC...

Nine consecutive isogenic Aspergillus fumigatus isolates cultured from a patient with aspergilloma were investigated for azole resistance. The first cultured isolate showed a wild-type phenotype, but four azole-resistant phenotypes were observed in the subsequent eight isolates. Four mutations were found in the cyp51A gene of these isolates, leading to the substitutions A9T, G54E, P216L, and F2...

Azole antifungals are used not only clinically for fungal infections but also used as agricultural fungicides. Recently, azole-resistant Aspergillus fumigatus containing a tandem repeat in the promoter region of cyp51A combined with amino acid substitution(s) appears in the environment in Eurasia, especially in several European countries. Although azole fungicides have been used in Japan, espec...

Acquired azole resistance in opportunistic fungi causes severe clinical problems in immunosuppressed individuals. This study investigated the molecular mechanisms of azole resistance in clinical isolates of Candida glabrata. Six unmatched strains were obtained from an epidemiological survey of candidiasis in immunocompromised hosts that included azole and amphotericin B susceptible and azole re...

Azole resistance in human fungal pathogens has increased over the past twenty years, especially in immunocompromised patients. Similarities between medical and agricultural azoles, and extensive azole (14α-demethylase inhibitor, DMI) use in crop protection, prompted speculation that resistance in patients with aspergillosis originated in the environment. Aspergillus species, and especially Aspe...

Infections due to Candida albicans are usually treated with azole antifungals such as fluconazole, but treatment failure is not uncommon especially in immunocompromised individuals. Relatedly, in vitro studies demonstrate that azoles are nonfungicidal, with continued growth at strain-dependent rates even at high azole concentrations. We hypothesized that upregulation of ERG11, which encodes the...

OBJECTIVES Resistance to azole antifungal drugs in Aspergillus fumigatus that is not mediated by target gene mutations is now common in some locations. The aim of this study was to investigate possible new mechanisms of resistance in non-target resistance. METHODS Twelve azole-resistant A. fumigatus isolates previously shown not to carry mutations in cyp51A were tested to determine whether th...

Azole antifungal agents (eg, fluconazole and itraconazole) have been widely used to treat superficial fungal infections caused by dermatophytes and, unlike the allylamines (such as terbinafine and naftifine), have been associated with resistance development. Although many published manuscripts describe resistance to azoles among yeast and molds, reports describing resistance of dermatophytes ar...