Biotechnology Research Center, Southwest University, Chongqing, China.
Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, United States.
Elife. 2023 Jul 4;12:e79179. doi: 10.7554/eLife.79179.
Mechanisms for cellular detoxification of drug compounds are of significant interest in human health. Cyclosporine A (CsA) and tacrolimus (FK506) are widely known antifungal and immunosuppressive microbial natural products. However, both compounds can result in significant side effects when used as immunosuppressants. The insect pathogenic fungus shows resistance to CsA and FK506. However, the mechanisms underlying the resistance have remained unknown. Here, we identify a P4-ATPase gene, , from the fungus, which confers resistance a unique vesicle mediated transport pathway that targets the compounds into detoxifying vacuoles. Interestingly, the expression of in plants promotes resistance to the phytopathogenic fungus via detoxification of the mycotoxin cinnamyl acetate using a similar pathway. Our data reveal a new function for a subclass of P4-ATPases in cell detoxification. The P4-ATPases conferred cross-species resistance can be exploited for plant disease control and human health protection.
细胞解毒药物化合物的机制在人类健康中具有重要意义。环孢菌素 A（CsA）和他克莫司（FK506）是广泛使用的抗真菌和免疫抑制微生物天然产物。然而，当用作免疫抑制剂时，这两种化合物都会导致严重的副作用。昆虫病原真菌 对 CsA 和 FK506 表现出抗性。然而，其抗性的机制仍不清楚。在这里，我们从真菌中鉴定出一个 P4-ATPase 基因 ，它赋予了对化合物进行解毒的独特囊泡介导的转运途径的抗性，将化合物靶向到解毒液泡中。有趣的是，在植物中表达 通过使用类似的途径将真菌毒素肉桂酸乙酯解毒，从而促进了对植物病原菌 的抗性。我们的数据揭示了 P4-ATPases 亚类在细胞解毒中的新功能。可以利用 P4-ATPases 赋予的跨物种抗性来控制植物病害和保护人类健康。
