The cdr1B efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in Aspergillus fumigatus
نویسندگان
چکیده
منابع مشابه
The cdr1B efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in Aspergillus fumigatus.
OBJECTIVES Recent increases in triazole resistance in Aspergillus fumigatus have been attributed primarily to target site (cyp51A) mutations. A recent survey of resistant isolates in Manchester showed that >50% of resistant isolates had no mutation in cyp51A or its promoter. We investigated the mechanisms of resistance in clinical azole-resistant isolates without cyp51A mutations. METHODS Twe...
متن کاملItraconazole resistance in Aspergillus fumigatus.
Invasive aspergillosis is an increasingly frequent opportunistic infection in immunocompromised patients. Only two agents, amphotericin B and itraconazole, are licensed for therapy. Itraconazole acts through inhibition of a P-450 enzyme undertaking sterol 14alpha demethylation. In vitro resistance in Aspergillus fumigatus to itraconazole correlated with in vivo outcome has not been previously d...
متن کاملA Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions
Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcript...
متن کاملAspergillus fumigatus strains with mutations in the cyp51A gene do not always show phenotypic resistance to itraconazole, voriconazole, or posaconazole.
We performed molecular identification of 98 Aspergillus fumigatus complex isolates with MICs of 1 to 4 μg/ml for itraconazole and searched for the presence of mutations in cyp51A. Most of the isolates (91%) belonged to A. fumigatus sensu stricto. We found 14 different mutations in nine isolates at codons different from G54, M220, G138, G448, and L98. We report new mutations at positions 165, 26...
متن کاملA point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus.
The genes encoding 14alpha-sterol demethylases (cyp51A and cyp51B) were analyzed in 12 itraconazole (ITC)-resistant and three ITC-susceptible clinical isolates of Aspergillus fumigatus. Six ITC-resistant strains exhibited a substitution of another amino acid for glycine at position 54, which is located at a very conserved region of the Cyp51A protein. The cyp51A gene from the A. fumigatus wild-...
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ژورنال
عنوان ژورنال: Journal of Antimicrobial Chemotherapy
سال: 2013
ISSN: 1460-2091,0305-7453
DOI: 10.1093/jac/dkt075