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Abstract Title:

Artemisinin elevates the ergosterol levels of Candida albicans to synergize with amphotericin B against oral candidiasis.

Abstract Source:

Int J Antimicrob Agents. 2021 Jun 28:106394. Epub 2021 Jun 28. PMID: 34197906

Abstract Author(s):

Chengguang Zhu, Binyou Liao, Xingchen Ye, Yujie Zhou, Xi Chen, Min Liao, Lei Cheng, Xuedong Zhou, Biao Ren

Article Affiliation:

Chengguang Zhu

Abstract:

Oral candidiasis, especially caused by Candida albicans, is the most common fungal infection in the oral cavity. The increase of drug resistance and lack of new antifungal agents call for new strategies of fungal treatment. This study repurposed artemisinin (Art) as a potentiator to amphotericin B (AmB) and characterized their synergistic mechanism against C. albicans and oral candidiasis. The synergistic antifungal activities between Art and AmB were identified through the checkerboard and recovered plate assays according to the fractional inhibitory concentration index (FICI). Art showed no antifungal ability even at>200 mg/L. However, it significantly reduced the AmB dosages against the wild-type strain and 75 clinical isolates of C. albicans (FICI<0.5). Art significantly upregulated the expression of genes from the ergosterol biosynthesis pathway (ERG1, ERG3, ERG9, and ERG11) as shown by qRT-PCR and elevated the ergosterol contents of Candida cells. Increased ergosterol contents significantly enhanced binding between fungal cells and the polyene agent, resulting in the sensitization of C. albicans to AmB. Drug combinations of Art and AmB showed synergistic capability against oral mucosal infection in vivo by reducing the epithelium infection area, fungal burden, and inflammatory infiltrates in murine oropharyngeal candidiasis. These findings indicate a novel synergistic antifungal drug combination and new Art mechanism of action, suggesting that drug reposition is a clinically practical way for antifungal drug development and treatment of oral candidiasis.

Study Type : In Vitro Study

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