Antifungal Activity and Potential Mechanism of 6,7, 4'-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans .

Autor:	Su LY; School of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, China., Ni GH; School of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, China.; Engineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Traditional Chinese Medicine, Kunming, China., Liao YC; School of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, China., Su LQ; School of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, China., Li J; School of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, China., Li JS; School of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, China., Rao GX; School of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, China.; Engineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Traditional Chinese Medicine, Kunming, China., Wang RR; School of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, China.; Engineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Traditional Chinese Medicine, Kunming, China.
Jazyk:	angličtina
Zdroj:	Frontiers in microbiology [Front Microbiol] 2021 Aug 17; Vol. 12, pp. 692693. Date of Electronic Publication: 2021 Aug 17 (Print Publication: 2021).
DOI:	10.3389/fmicb.2021.692693
Abstrakt:	The increased resistance of Candida albicans to conventional antifungal drugs poses a huge challenge to the clinical treatment of this infection. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. This study assessed the effect of 6,7,4'-O-triacetylscutellarein (TA) combined with fluconazole (FLC) on C. albicans in vitro and in vivo . TA combined with FLC showed good synergistic antifungal activity against drug-resistant C. albicans in vitro , with a partial inhibitory concentration index (FICI) of 0.0188-0.1800. In addition, the time-kill curve confirmed the synergistic effect of TA and FLC. TA combined with FLC showed a strong synergistic inhibitory effect on the biofilm formation of resistant C. albicans . The combined antifungal efficacy of TA and FLC was evaluated in vivo in a mouse systemic fungal infection model. TA combined with FLC prolonged the survival rate of mice infected with drug-resistant C. albicans and reduced tissue invasion. TA combined with FLC also significantly inhibited the yeast-hypha conversion of C. albicans and significantly reduced the expression of RAS-cAMP-PKA signaling pathway-related genes (RAS1 and EFG1) and hyphal-related genes (HWP1 and ECE1). Furthermore, the mycelium growth on TA combined with the FLC group recovered after adding exogenous db-cAMP. Collectively, these results show that TA combined with FLC inhibits the formation of hyphae and biofilms through the RAS-cAMP-PKA signaling pathway, resulting in reduced infectivity and resistance of C. albicans . Therefore, this study provides a basis for the treatment of drug-resistant C. albicans infections. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Su, Ni, Liao, Su, Li, Li, Rao and Wang.)
Databáze:	MEDLINE
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