Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of Shikonin
Development of antifungal agents with novel mechanism and low toxicity are essential due to the prevalence of the infectious diseases caused by Candida albicans. The current study employed a new research method, which combined the ultra-high performance liquid chromatography with quadrupole time-of-...
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1657362 |
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| author | ZeBin Liao ZhenYu Zhu Ling Li Liang Wang Hui Wang YuanYing Jiang YingYing Cao |
| author_facet | ZeBin Liao ZhenYu Zhu Ling Li Liang Wang Hui Wang YuanYing Jiang YingYing Cao |
| author_sort | ZeBin Liao |
| collection | DOAJ |
| description | Development of antifungal agents with novel mechanism and low toxicity are essential due to the prevalence of the infectious diseases caused by Candida albicans. The current study employed a new research method, which combined the ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and gas chromatography-mass spectrometry, to investigate the intrinsic mechanism of Shikonin (SK) against C. albicans. The levels of 27 metabolites, which mainly involved in histone deacetylation, amino acid synthesis, lipid synthesis, nitrogen metabolism, tricarboxylic acid cycle, oxidative stress and glycolysis, were remarkably changed upon SK treatment. Specially, the down-regulation of nicotinamide (NAM) upon SK treatment indicated the suppression of the deacetylation of the histone H3 on lysine 56 residue (H3K56). Further experiment confirmed that the level of H3K56 acetylation (H3K56ac) was dramatically increased upon SK treatment which was mediated by HST3, the gene encoding the H3K56 deacetylase (Hst3p). Our results demonstrated that SK is the first natural compound reported to execute antifungal activity directly via boosting H3K56ac mediated by HST3. Importantly, this finding shed new light on the mechanisms to relieve the side effects or reverse the drug tolerance, as well as the development of agents for antifungal therapies. |
| format | Article |
| id | doaj-art-5c13d01c6c2d4f3d97508ecf27ed0bde |
| institution | DOAJ |
| issn | 2222-1751 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-5c13d01c6c2d4f3d97508ecf27ed0bde2025-08-20T03:17:55ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-01811243125310.1080/22221751.2019.1657362Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of ShikoninZeBin Liao0ZhenYu Zhu1Ling Li2Liang Wang3Hui Wang4YuanYing Jiang5YingYing Cao6Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, People’s Republic of ChinaSchool of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of ChinaSchool of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of ChinaSchool of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of ChinaSchool of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaShanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDevelopment of antifungal agents with novel mechanism and low toxicity are essential due to the prevalence of the infectious diseases caused by Candida albicans. The current study employed a new research method, which combined the ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and gas chromatography-mass spectrometry, to investigate the intrinsic mechanism of Shikonin (SK) against C. albicans. The levels of 27 metabolites, which mainly involved in histone deacetylation, amino acid synthesis, lipid synthesis, nitrogen metabolism, tricarboxylic acid cycle, oxidative stress and glycolysis, were remarkably changed upon SK treatment. Specially, the down-regulation of nicotinamide (NAM) upon SK treatment indicated the suppression of the deacetylation of the histone H3 on lysine 56 residue (H3K56). Further experiment confirmed that the level of H3K56 acetylation (H3K56ac) was dramatically increased upon SK treatment which was mediated by HST3, the gene encoding the H3K56 deacetylase (Hst3p). Our results demonstrated that SK is the first natural compound reported to execute antifungal activity directly via boosting H3K56ac mediated by HST3. Importantly, this finding shed new light on the mechanisms to relieve the side effects or reverse the drug tolerance, as well as the development of agents for antifungal therapies.https://www.tandfonline.com/doi/10.1080/22221751.2019.1657362MetabonomicsCandida albicansShikoninhyperacetylation of the histone H3K56HST3 |
| spellingShingle | ZeBin Liao ZhenYu Zhu Ling Li Liang Wang Hui Wang YuanYing Jiang YingYing Cao Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of Shikonin Emerging Microbes and Infections Metabonomics Candida albicans Shikonin hyperacetylation of the histone H3K56 HST3 |
| title | Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of Shikonin |
| title_full | Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of Shikonin |
| title_fullStr | Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of Shikonin |
| title_full_unstemmed | Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of Shikonin |
| title_short | Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of Shikonin |
| title_sort | metabonomics on candida albicans indicate the excessive h3k56ac is involved in the antifungal activity of shikonin |
| topic | Metabonomics Candida albicans Shikonin hyperacetylation of the histone H3K56 HST3 |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1657362 |
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