Gain-of-Function Mutations in UPC2 Are a Frequent Cause of ERG11 Upregulation in Azole-Resistant Clinical Isolates of Candida albicans

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Nucleotide substitutions in the Candida albicans ERG11 gene of azole-susceptible and azole-resistant clinical isolates.

One of the mechanisms of Candida albicans resistance to azole drugs used in antifungal therapy relies on increased expression and presence of point mutations in the ERG11 gene that encodes sterol 14α demethylase (14DM), an enzyme which is the primary target for the azole class of antifungals. The aim of the study was to analyze nucleotide substitutions in the Candida albicans ERG11 gene of azol...

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MUTATION IN HOTSPOT REGIONS OF THE ERG11 GENE AND FLUCONAZOLE RESISTANCE IN CLINICAL ISOLATES OF CANDIDA ALBICANS IN RASHT CITY

Background & Aims: Nowadays, the common use of azoles has led to increased resistance to azole among Candida albicans strains. Amino acid substitutions in azole target enzyme, ERG11p, is attributed to azole resistance in some clinical strains of Candida albicans. The aim of this study was to evaluate ERG11 gene mutations in fluconazole-resistant isolates of Candida albicans in Rasht. Materials...

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A gain-of-function mutation in the transcription factor Upc2p causes upregulation of ergosterol biosynthesis genes and increased fluconazole resistance in a clinical Candida albicans isolate.

In the pathogenic yeast Candida albicans, the zinc cluster transcription factor Upc2p has been shown to regulate the expression of ERG11 and other genes involved in ergosterol biosynthesis upon exposure to azole antifungals. ERG11 encodes lanosterol demethylase, the target enzyme of this antifungal class. Overexpression of UPC2 reduces azole susceptibility, whereas its disruption results in hyp...

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Contribution of clinically derived mutations in ERG11 to azole resistance in Candida albicans.

In Candida albicans, the ERG11 gene encodes lanosterol demethylase, the target of the azole antifungals. Mutations in ERG11 that result in an amino acid substitution alter the abilities of the azoles to bind to and inhibit Erg11, resulting in resistance. Although ERG11 mutations have been observed in clinical isolates, the specific contributions of individual ERG11 mutations to azole resistance...

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ژورنال

عنوان ژورنال: Eukaryotic Cell

سال: 2012

ISSN: 1535-9778,1535-9786

DOI: 10.1128/ec.00215-12