Multidrug resistance in Aspergillus nidulans involves novel ATP-binding cassette transporters

被引：106

作者：

Del Sorbo G. ^{[1
,3
,4
]}

Andrade A.C. ^{[1
]}

Van Nistelrooy J.G.M. ^{[1
]}

Van Kan J.A.L. ^{[1
]}

Balzi E. ^{[2
]}

De Waard M.A. ^{[1
]}

机构：

[1] Department of Phytopathology, Wageningen Agricultural University, 6700 EE Wageningen

[2] U. de Biochimie Physiologique, Univ. Catholique de Louvain, B-1348 Louvain-la-Neuve

[3] Institute of Plant Pathology, University of Naples Federico II, 80055 Portici, Naples

来源：

Molecular and General Genetics MGG | 1997年 / 254卷 / 4期

关键词：

ABC transporters; Drug efflux; Filamentous fungi; Fungicides; PDR5; complementation; Sterol 14α-demethylation inhibitors;

D O I：

10.1007/s004380050434

中图分类号：

学科分类号：

摘要：

Two single-copy genes, designated atrA and atrB (ATP-binding cassette transporter A and B), were cloned from the filamentous fungus Aspergillus nidulans and sequenced. Based on the presence of conserved motifs and on hydropathy analysis, the products encoded by atrA and atrB can be regarded as novel members of the ATP-binding cassette (ABC) superfamily of membrane transporters. Both products share the same topology as the ABC transporters PDR5 and SNQ2 from Saccharomyces cerevisiae and CDR1 from Candida albicans, which are involved in multidrug resistance of these yeasts. Significant homology also occurs between the ATP-binding cassettes of AtrA and AtrB, and those of mammalian ABC transporters (P-glycoproteins). The transcription of atrA and, in particular, atrB in mycelium of A. nidulans is strongly enhanced by treatment with several drugs, including antibiotics, azole fungicides and plant defense toxins. The enhanced transcription is detectable within a few minutes after drug treatment and coincides with the beginning of energy-dependent drug efflux activity, reported previously in the fungus for azole fungicides. Transcription of the atr genes has been studied in a wild-type and in a series of isogenic strains carrying the imaA and/or imaB genes, which confer multidrug resistance to various toxic compounds such as the azole fungicide imazalil. atrB is constitutively transcribed at a low level in the wild-type and in strains carrying imaA or imaB. Imazalil treatment enhances transcription of atrB to a similar extent in all strains tested. atrA, unlike atrB, displays a relatively high level of constitutive expression in mutants carrying imaB. Imazalil enhances transcription of atrA more strongly in imaB mutants, suggesting that the imaB locus regulates atrA. Functional analysis demonstrated that cDNA of atrB can complement the drug hypersensitivity associated with PDR5 deficiency in S. cerevisiae.

引用

页码：417 / 426

页数：9

共 61 条

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