Multiple Resistance Mechanisms among Aspergillus fumigatus Mutants with High-Level Resistance to Itraconazole

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Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole.

A collection of Aspergillus fumigatus mutants highly resistant to itraconazole (RIT) at 100 micro g ml(-1) were selected in vitro (following UV irradiation as a preliminary step) to investigate mechanisms of drug resistance in this clinically important pathogen. Eight of the RIT mutants were found to have a mutation at Gly54 (G54E, -K, or -R) in the azole target gene CYP51A. Primers designed fo...

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Itraconazole 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...

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Multiple mechanisms contribute to the development of clinically significant azole resistance in Aspergillus fumigatus

Infections caused by the filamentous fungus Aspergillus fumigatus are a significant clinical issue and represent the second most-common form of fungal infection. Azole drugs are effective against this pathogen but resistant isolates are being found more frequently. Infections associated with azole resistant A. fumigatus have a significantly increased mortality making understanding drug resistan...

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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...

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Morphological changes and induction of antifungal resistance in Aspergillus fumigatus due to different CO2 levels

Background and Purpose: Aspergillosis is one of the most common opportunistic fungal infections in immunocompromised and neutropenic patients. Aspergillus fumigatus (A. fumigatus) is the most common causative agent of this infection. Due to variable CO2 concentrations that pathogens are exposed to during the infection process and to understand the role of CO2, we examined the effects of various...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2003

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.47.5.1719-1726.2003