Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans
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...
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| Format: | Article |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.692693/full |
| _version_ | 1819137241530761216 |
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| author | Liu-Yan Su Guang-Hui Ni Guang-Hui Ni Yi-Chuan Liao Liu-Qing Su Jun Li Jia-Sheng Li Gao-Xiong Rao Gao-Xiong Rao Rui-Rui Wang Rui-Rui Wang |
| author_facet | Liu-Yan Su Guang-Hui Ni Guang-Hui Ni Yi-Chuan Liao Liu-Qing Su Jun Li Jia-Sheng Li Gao-Xiong Rao Gao-Xiong Rao Rui-Rui Wang Rui-Rui Wang |
| author_sort | Liu-Yan Su |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T10:47:45Z |
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| id | doaj.art-f78fbe235cbd4927b82bd9d38a0b3e86 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T10:47:45Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-f78fbe235cbd4927b82bd9d38a0b3e862022-12-21T18:28:54ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-08-011210.3389/fmicb.2021.692693692693Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicansLiu-Yan Su0Guang-Hui Ni1Guang-Hui Ni2Yi-Chuan Liao3Liu-Qing Su4Jun Li5Jia-Sheng Li6Gao-Xiong Rao7Gao-Xiong Rao8Rui-Rui Wang9Rui-Rui Wang10School of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaSchool of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaEngineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaSchool of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaSchool of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaSchool of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaSchool of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaSchool of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaEngineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaSchool of Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaEngineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Traditional Chinese Medicine, Kunming, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fmicb.2021.692693/fullCandida albicansdrug resistance674′-O-triacetylscutellareinfluconazole |
| spellingShingle | Liu-Yan Su Guang-Hui Ni Guang-Hui Ni Yi-Chuan Liao Liu-Qing Su Jun Li Jia-Sheng Li Gao-Xiong Rao Gao-Xiong Rao Rui-Rui Wang Rui-Rui Wang Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans Frontiers in Microbiology Candida albicans drug resistance 6 7 4′-O-triacetylscutellarein fluconazole |
| title | Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans |
| title_full | Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans |
| title_fullStr | Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans |
| title_full_unstemmed | Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans |
| title_short | Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans |
| title_sort | antifungal activity and potential mechanism of 6 7 4 o triacetylscutellarein combined with fluconazole against drug resistant c albicans |
| topic | Candida albicans drug resistance 6 7 4′-O-triacetylscutellarein fluconazole |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.692693/full |
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