کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10801968 | 1055649 | 2015 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Tfp1 is required for ion homeostasis, fluconazole resistance and N-Acetylglucosamine utilization in Candida albicans
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
The vacuolar-type H+-ATPase (V-ATPase) is crucial for the maintenance of ion homeostasis. Dysregulation of ion homeostasis affects various aspects of cellular processes. However, the importance of V-ATPase in Candida albicans is not totally clear. In this study, we demonstrated the essential roles of V-ATPase through Tfp1, a putative V-ATPase subunit. Deletion of TFP1 led to generation of an iron starvation signal and reduced total iron content, which was associated with mislocalization of Fet34p that was finally due to disorders in copper homeostasis. Furthermore, the tfp1â/â mutant exhibited weaker growth and lower aconitase activity on nonfermentable carbon sources, and iron or copper addition partially rescued the growth defect. In addition, the tfp1â/â mutant also showed elevated cytosolic calcium levels in normal or low calcium medium that were relevant to calcium release from vacuole. Kinetics of cytosolic calcium response to an alkaline pulse and VCX1 (VCX1 encodes a putative vacuolar Ca2Â +/H+ exchanger) overexpression assays indicated that the cytosolic calcium status was in relation to Vcx1 activity. Spot assay and concentration-kill curve demonstrated that the tfp1â/â mutant was hypersensitive to fluconazole, which was attributed to reduced ergosterol biosynthesis and CDR1 efflux pump activity, and iron/calcium dysregulation. Interestingly, carbon source utilization tests found the tfp1â/â mutant was defective for growth on N-Acetylglucosamine (GlcNAc) plate, which was associated with ATP depletion due to the decreased ability to catabolize GlcNAc. Taken together, our study gives new insights into functions of Tfp1, and provides the potential to better exploit V-ATPase as an antifungal target.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1853, Issue 10, Part A, October 2015, Pages 2731-2744
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1853, Issue 10, Part A, October 2015, Pages 2731-2744
نویسندگان
Chang Jia, Kai Zhang, Qilin Yu, Bing Zhang, Chenpeng Xiao, Yijie Dong, Yulu Chen, Biao Zhang, Laijun Xing, Mingchun Li,