ABC transporters coupled with the elevated ergosterol contents contribute to the azole resistance and amphotericin B susceptibility----中国科学院微生物研究所

科研成果

论文题目:	ABC transporters coupled with the elevated ergosterol contents contribute to the azole resistance and amphotericin B susceptibility
作者:	Ren Biao, Dai Huan-Qin, Pei Gang, Tong Yao-Jun, Zhuo Ying, Yang Na, Su Meng-Yi, Huang Pei, Yang Yu-Zhuo, Zhang Li-Xin*
联系作者:	Zhang Li-Xin*
刊物名称:	Appl Microbiol Biotechnol
期:	98
卷:	6
页:	2609-16
年份:	2014
影响因子:	3.762
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摘要:	Most screening approaches produce compounds that target survival genes and are likely to generate resistance over time. Simply having more drugs does not address the potential emergence of resistance caused by target mutation, drug efflux pumps over-expression, and so on. There is a great need to explore new strategies to treat fungal infections caused by drug-resistant pathogens. In this study, we found that azole-resistant Candida albicans with CaCDR1 and CaCDR2 over-expression is hypersensitive against amphotericin B (AmB) by our high throughput synergy screening (HTSS). In contrast, Deltacdr1 and Deltacdr2 knockout strains were resistant to AmB. Moreover, clinical isolates with increased expression of CaCDR1 and CaCDR2 demonstrated susceptibility to AmB, which can also synergize with the efflux pumps inducer fluphenazine (FPZ). Finally, the increased drug susceptibility to AmB in azole-resistant C. albicans with drug efflux pumps over-expression was consistent with the elevated expression of CaERG11 and its associated ergosterols in clinical isolates. Our data implies that the level of ergosterol contents determines the susceptibility to azoles and AmB in C. albicans. Deep understanding of the above mechanisms would offer new hope to treat drug-resistant C. albicans.