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Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma
Chen, J; Li, HM; Li, RY; Bu, DF; Wan, Z
关键词azole antifungals resistance genetics MICs
刊名JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
2005
DOI10.1093/jac/dkh507
55期:1页:31-37
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy
研究领域[WOS]Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy
关键词[WOS]IN-VITRO SUSCEPTIBILITY ; POLYMORPHIC DNA ; MOLECULAR EPIDEMIOLOGY ; INVASIVE ASPERGILLOSIS ; REDUCED SUSCEPTIBILITY ; RANDOM AMPLIFICATION ; RESISTANCE ; MECHANISMS ; SEQUENCE ; MUTANTS
英文摘要

Objectives: To monitor changes in itraconazole susceptibility of isolates from a patient undergoing treatment for pulmonary Aspergillus infection and relate these changes to genotypic/phenotypic alterations.

Methods: Six Aspergillus fumigatus isolates were serially recovered from the patient. Itraconazole MICs were determined by Etest and NCCLS methodology. Growth characteristics and phenotype were monitored. Molecular analysis included random amplified polymorphic DNA (RAPD) assay and sequencing of the cyp51A gene.

Results: The MIC of itraconazole against the first isolate before treatment was 0.25 mg/L; the MIC against the second isolate, recovered after 6 months of itraconazole therapy, was >16 mg/L; and that against the third isolate, obtained 2 months after discontinuation of the therapy, was 0.5 mg/L. The MIC against the last three isolates, acquired after restoration of itraconazole therapy for 4-7 months, was >16 mg/L. The six isolates shared identical band patterns of RAPD assay using four primers and the same sequence in intertranscribed spacers (ITS). Therefore, the six isolates were likely to be the same strain of A. fumigatus, and mutations involving itraconazole resistance possibly occurred in these isolates after prolonged itraconazole therapy. Sequencing of the cyp51A gene in the coding region revealed a mutation of M220I in cytochrome P450 sterol 14-alpha-demethylase in the second resistant isolate and a mutation of G54R in the last three resistant isolates. Expression changes of some pump genes, such as MDR3, may also, in part, be related to the resistance to itraconazole.

Conclusions: We conclude that resistance of A. fumigatus to itraconazole occurred in a patient treated with the drug, and the resistance may result from mutations in the cyp51A gene-the gene encoding the target enzyme for itraconazole.

语种英语
WOS记录号WOS:000226309100005
引用统计
被引频次:108[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58581
专题北京大学第一临床医学院_皮肤性病科
作者单位Peking Univ, Peking Univ Hosp 1, Res Ctr Med Mycol, Dept Dermatol, Beijing 100034, Peoples R China
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GB/T 7714
Chen, J,Li, HM,Li, RY,et al. Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma[J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY,2005,55(1):31-37.
APA Chen, J,Li, HM,Li, RY,Bu, DF,&Wan, Z.(2005).Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma.JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY,55(1),31-37.
MLA Chen, J,et al."Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma".JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 55.1(2005):31-37.
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