https://scholars.lib.ntu.edu.tw/handle/123456789/606128
標題: | Natural alkaloid tryptanthrin exhibits novel anticryptococcal activity | 作者: | Lin C.-J Chang Y.-L Yang Y.-L YING-LIEN CHEN |
關鍵字: | antifungal agent;Cryptococcus;fungal pathogen;natural product;tryptanthrin;alkaloid derivative;amphotericin B;cyclic AMP dependent protein kinase;cyclosporine;fluconazole;tacrolimus;unclassified drug;antifungal activity;Article;controlled study;cryptococcosis;Cryptococcus neoformans;drug potentiation;G1 phase cell cycle checkpoint;in vitro study;minimum inhibitory concentration;nonhuman;S phase cell cycle checkpoint;signal transduction;Trichophyton rubrum;Trichophyton rubrum infection | 公開日期: | 2021 | 卷: | 59 | 期: | 6 | 起(迄)頁: | 545-556 | 來源出版物: | Medical Mycology | 摘要: | Cryptococcal meningitis is a prevalent invasive fungal infection that causes around 180 000 deaths annually. Currently, treatment for cryptococcal meningitis is limited and new therapeutic options are needed. Historically, medicinal plants are used to treat infectious and inflammatory skin infections. Tryptanthrin is a natural product commonly found in these plants. In this study, we demonstrated that tryptanthrin had antifungal activity with minimum inhibitory concentration (MIC) of 2 μg/ml against Cryptococcus species and of 8 μg/ml against Trichophyton rubrum. Further analysis demonstrated that tryptanthrin exerted fungistatic and potent antifungal activity at elevated temperature. In addition, tryptanthrin exhibited a synergistic effect with the calcineurin inhibitors FK506 and cyclosporine A against Cryptococcus neoformans. Furthermore, our data showed that tryptanthrin induced cell cycle arrest at the G1/S phase by regulating the expression of genes encoding cyclins and the SBF/MBF complex (CLN1, MBS1, PCL1, and WHI5) in C. neoformans. Screening of a C. neoformans mutant library further revealed that tryptanthrin was associated with various transporters and signaling pathways such as the calcium transporter (Pmc1) and protein kinase A signaling pathway. In conclusion, tryptanthrin exerted novel antifungal activity against Cryptococcus species through a mechanism that interferes with the cell cycle and signaling pathways. ? 2020 The Author(s). Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85108204226&doi=10.1093%2fmmy%2fmyaa074&partnerID=40&md5=28d1e6095f3789fc0ff1e2e874316d76 https://scholars.lib.ntu.edu.tw/handle/123456789/606128 |
ISSN: | 13693786 | DOI: | 10.1093/mmy/myaa074 |
顯示於: | 植物病理與微生物學系 |
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