CalPF14030 negatively modulates intracellular ATP levels during the development of azole resistance in Candida albicans

Aim: Widespread and repeated use of azoles, particularly fluconazole, has led to the rapid development of azole resistance in Candida albicans. We investigated the role of CalPF14030 during the development of azole resistance in C albicans. Methods: The expression of CalPF14030 was measured by quant...

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Veröffentlicht in:中国药理学报:英文版 2011, Vol.32 (4), p.512-518
1. Verfasser: Xin-ming JIA Ying WANG Jun-dong ZHANG Hong-yue TAN Yuan-yingJIANG Jun GU
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Sprache:eng
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Zusammenfassung:Aim: Widespread and repeated use of azoles, particularly fluconazole, has led to the rapid development of azole resistance in Candida albicans. We investigated the role of CalPF14030 during the development of azole resistance in C albicans. Methods: The expression of CalPF14030 was measured by quantitative RT-PCR, and CalPF14030 was disrupted by the hisG-URA3- hisG (URA-blaster) method. The sensitivity of C albicans to azoles was examined using a spot assay, and the intracellular ATP concen- trations were measured by a luminometer. Results: CalPF14030 expression in C albicans was up-regulated by Ca2+ in a calcineurin-dependent manner, and the protein was overexpressed during the stepwise acquisition of azole resistance. However, disruption or ectopic overexpression of CalPF14030 did not affect the sensitivity of C albicans to azoles. Finally, we demonstrated that disruption of CalPF14030 significantly increased intracellular ATP levels, and overexpression significantly decreased intracellular ATP levels in C albicans. Conclusion: CalPF14030 may negatively modulate intracellular ATP levels during the development of azole resistance in C albicans.
ISSN:1671-4083
1745-7254