The in vitro activity of three different azoles (fluconazole, FLC, voriconazole, VRC and ketoconazole, KTC) was determined and correlated with the single nucleotide polymorphisms (SNPs) in a “hot spot” region of the ERG11 gene in a collection of 52 arbitrarily selected C. albicans strains isolated from Sardinian subjects with oropharyngeal candidiasis. Among the strains evaluated, 23.1% were re...

Background Candida parapsilosis is one of the five common strains of yeasts involved in invasive candidiasis. The expression analysis of sterol biosynthesis pathway genes, which are associated with resistance, can assist the better understanding of antifungal resistance mechanisms. Method The antifungal susceptibility of 120 clinical C. parapsilosis isolates was examined. The changes in the g...

Background and Purpose: The frequency of opportunistic fungal infections in immunocompromised patients, especially by Candida species, has sharply increased in the last few decades. The objective of this study was to analyse the ergosterol content and gene expression profiling of clinical isolates of fluconazole resistant Candida albicans. Materials and Methods: Sixty clinical samples were ide...

The leading fungal pathogens causing systemic infections in humans are Candida spp., Aspergillus fumigatus , and Cryptococcus neoformans . major class of antifungals used to treat such the triazoles, which target cytochrome P450 lanosterol 14-α-demethylase, encoded by ERG11 (yeasts)/ cyp51A (molds) genes, catalyzing a key step ergosterol biosynthetic pathway. Triazole resistance clinical fungi ...

UNLABELLED Ergosterol is a major and specific component of the fungal plasma membrane, and thus, the cytochrome P450 enzymes (Erg proteins) that catalyze ergosterol synthesis have been selected as valuable targets of azole antifungals. However, the opportunistic pathogen Aspergillus fumigatus has developed worldwide resistance to azoles largely through mutations in the cytochrome P450 enzyme Cy...

Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans. To better understand Upc2p function in C. albicans, we used genomewide location profiling to identify the transcriptional targets of Upc2p in vivo. A triple hemagglutinin epitope, introduced at the C terminus of Upc2p, conferred a gain-of-func...

Candida glabrata has emerged as a common cause of fungal infection. This yeast has intrinsically low susceptibility to azole antifungals such as fluconazole, and mutation to frank azole resistance during treatment has been documented. Potential resistance mechanisms include changes in expression or sequence of ERG11 encoding the azole target. Alternatively, resistance could result from upregula...

In this study, we present a rare case of fatal breakthrough Candida tropicalis infection in a patient with acute lymphoblastic leukemia (ALL) while on posaconazole prophylaxis. Then, we explore the mechanisms underlying azole resistance by focusing on enhanced efflux pumps and changes in the azole target enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that Y132C subst...

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...