期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 58, 期 3, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijantimicag.2021.106394
关键词
Candida albicans; Oral candidiasis; Traditional Chinese medicine; Drug repurposing; Synergy; Combination
资金
- National Natural Science Foundation of China [81870778, 81600858, 81870759]
- Applied Basic Research Programs of Sichuan Province [2020YJ0227]
- Youth Grant of the Science and Technology Department of Sichuan Province, China [2017JQ0028]
- Innovative Research Team Program of Sichuan Province
The study found that artemisinin could synergize with amphotericin B to combat Candida albicans and oral candidiasis, increasing ergosterol content in yeast cells to enhance binding between drugs and cells, reducing epithelial infection area and fungal burden in the oral cavity.
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 anti fungal 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. (c) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.
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