An A643T Mutation in the Transcription Factor Upc2p Causes Constitutive ERG11 Upregulation and Increased Fluconazole Resistance in Candida albicans

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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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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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The new mutation L321F in Candida albicans ERG11 gene may be associated with fluconazole resistance.

BACKGROUND For many years fluconazole has been commonly used to treat Candida infections. However, the indiscriminate use of this antimycotic therapy has favored the emergence of resistant isolates. Mutations in the ERG11 gene have been described as one of the primary mechanisms of resistance in Candida species. AIMS In this study we investigated missense mutations in ERG11 genes of Candida a...

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Role of Candida albicans transcription factor Upc2p in drug resistance and sterol metabolism.

In Candida albicans, drug resistance to clinically important antifungal drugs may be regulated through the action of transcription factors in a manner that may or may not be similar to regulation in Saccharomyces cerevisiae. A search of the C. albicans genome identified a single homolog of the S. cerevisiae transcription factor genes UPC2 (ScUPC2) and ECM22 (ScECM22) that have been associated w...

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Quantitation of ergosterol content and gene expression profile of ERG11 gene in fluconazole-resistant Candida albicans

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...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2010

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.01102-09