有哪些信誉好的足球投注网站antagonistic changes in sensitivity to antifungal drugs by mutations of an important abc transporter gene in a fungal pathogen敌对的抗真菌药物敏感性的变化中的一个重要abc转运蛋白基因突变的真菌病原体.pdfVIP
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Antagonistic Changes in Sensitivity to Antifungal Drugs
by Mutations of an Important ABC Transporter Gene in a
Fungal Pathogen
1,2 2 1 3 4 1
Wenjun Guan , Huifeng Jiang , Xiaoxian Guo , Eugenio Mancera , Lin Xu , Yudong Li , Lars
3 1 2
Steinmetz , Yongquan Li *, Zhenglong Gu *
1 College of Life Sciences, Zhejiang University, Hangzhou, People’s Republic of China, 2 Division of Nutritional Sciences, Cornell University, Ithaca, New York, United States
of America, 3 European Molecular Biology Laboratory, Heidelberg, Germany, 4 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United
States of America
Abstract
Fungal pathogens can be lethal, especially among immunocompromised populations, such as patients with AIDS and
recipients of tissue transplantation or chemotherapy. Prolonged usage of antifungal reagents can lead to drug resistance
and treatment failure. Understanding mechanisms that underlie drug resistance by pathogenic microorganisms is thus vital
for dealing with this emerging issue. In this study, we show that dramatic sequence changes in PDR5, an ABC (ATP-binding
cassette) efflux transporter protein gene in an opportunistic fungal pathogen, caused the organism to become
hypersensitive to azole, a widely used antifungal drug. Surprisingly, the same mutations conferred growth advantages to
the organism on polyenes, which are also commonly used antimycotics. Our results indicate that Pdr5p might be important
for ergosterol homeostasis. The observed remarkable sequence divergence in the PDR5 gene in yeast strain YJM789 may
represent an interesting case of adaptive loss of gene function with significant clin
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