In Vivo Emergence of Aspergillus terreus with Reduced Azole Susceptibility and a Cyp51a M217I Alteration

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In vivo emergence of Aspergillus terreus with reduced azole susceptibility and a Cyp51a M217I alteration.

Azole resistance in Aspergillus terreus isolates was explored. Twenty related (MB) and 6 unrelated A. terreus isolates were included. CYP51A sequencing and RAPD genotyping was performed. Five MB isolates were itraconazole susceptible, whereas the minimum inhibitory concentrations (MICs) for 15 MB isolates were elevated (1-2 mg/L). Voriconazole and posaconazole MICs were 0.5-4 and 0.06-0.5 mg/L,...

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cyp51A-based mechanisms of Aspergillus fumigatus azole

72 Since the mid-1990s, a steady increase in the occurrence of itraconazole resistant Aspergillus 73 fumigatus isolates has been observed in clinical contexts leading to therapeutic failure in the 74 treatment of aspergillosis. This increase has been predominantly linked to a single allele of 75 the cyp51A gene, termed ‘TR/L98H’ which is thought to have arisen through the use of 76 agricultural...

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In Vitro Activity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms.

ASP2397 is a new compound with a novel and as-yet-unknown target different from that of licensed antifungal agents. It has activity against Aspergillus and Candida glabrata. We compared its in vitro activity against wild-type and azole-resistant A. fumigatus and A. terreus isolates with that of amphotericin B, itraconazole, posaconazole, and voriconazole. Thirty-four isolates, including 4 wild-...

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Targeted gene disruption of the 14-alpha sterol demethylase (cyp51A) in Aspergillus fumigatus and its role in azole drug susceptibility.

The role of Aspergillus fumigatus 14alpha-sterol demethylase (Cyp51A) in azole drug susceptibility was assessed. Targeted disruption of cyp51A in azole-susceptible and -resistant strains decreased MICs from 2- to 40-fold. The cyp51A mutants were morphologically indistinguishable from the wild-type strain, retaining the ability to cause pulmonary disease in neutropenic mice.

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Multiple cyp51A-based mechanisms identified in azole-resistant isolates of Aspergillus fumigatus from China.

Seventy-two A. fumigatus clinical isolates from China were investigated for azole resistance based on mutations of cyp51A. We identified four azole-resistant strains, among which we found three strains highly resistant to itraconazole, two of which exhibit the TR34/L98H/S297T/F495I mutation, while one carries only the TR34/L98H mutation. To our knowledge, the latter has not been found previousl...

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ژورنال

عنوان ژورنال: The Journal of Infectious Diseases

سال: 2012

ISSN: 1537-6613,0022-1899

DOI: 10.1093/infdis/jis442