白色念珠菌
两性霉素B
麦角甾醇
白色体
青蒿素
微生物学
药理学
抗真菌药
体内
抗药性
咪康唑
生物
免疫学
抗真菌
生物化学
恶性疟原虫
生物技术
疟疾
作者
C. G. Zhu,Binyou Liao,Xingchen Ye,Yujie Zhou,Xi Chen,Min Liao,Lei Cheng,Xuedong Zhou,Biao Ren
标识
DOI:10.1016/j.ijantimicag.2021.106394
摘要
Oral candidiasis, especially caused by Candida albicans, is the most common fungal infection of the oral cavity. The increase in drug resistance and lack of new antifungal agents call for new strategies of antifungal treatment. This study repurposed artemisinin (Art) as a potentiator to the polyene amphotericin B (AmB) and characterised their synergistic mechanism against C. albicans and oral candidiasis. The synergistic antifungal activity between Art and AmB was identified by the checkerboard and recovery plate assays according to the fractional inhibitory concentration index (FICI). Art showed no antifungal activity even at >200 mg/L. However, it significantly reduced AmB dosages against the wild-type strain and 75 clinical isolates of C. albicans (FICI ≤ 0.5). Art significantly upregulated expression of genes from the ergosterol biosynthesis pathway (ERG1, ERG3, ERG9 and ERG11), as shown by RT-qPCR, and elevated the ergosterol content of Candida cells. Increased ergosterol content significantly enhanced binding between fungal cells and the polyene agent, resulting in sensitisation of C. albicans to AmB. Drug combinations of Art and AmB showed synergistic activity against oral mucosal infection in vivo by reducing the epithelial infection area, fungal burden and inflammatory infiltrates in murine oropharyngeal candidiasis. These findings indicate a novel synergistic antifungal drug combination and a new Art mechanism of action, suggesting that drug repurposing is a clinically practical means of antifungal drug development and treatment of oral candidiasis.
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