脂肽
枯草芽孢杆菌
抗真菌
化学
钾通道
钾
离子通道
环肽
生物化学
微生物学
生物物理学
细菌
生物
有机化学
肽
受体
遗传学
作者
Saixue Yang,Y.T. Ji,Pengyuan Xue,Zhenzhu Li,Xianqing Chen,Junling Shi,Chunmei Jiang
标识
DOI:10.1016/j.ijbiomac.2024.134306
摘要
Fungal infections pose severe and potentially lethal threats to plant, animal, and human health. Ergosterol has served as the primary target for developing antifungal medications. However, many antifungal drugs remain highly toxic to humans due to similarity in cell membrane composition between fungal and animal cells. Iturin A, lipopeptide produced by Bacillus subtilis, efficiently inhibit various fungi, but demonstrated safety in oral administration, indicating the existence of targets different from ergosterol. To pinpoint the exact antifungal target of iturin A, we used homologous recombination to knock out and overexpress erg3, a key gene in ergosterol synthesis. Saccharomyces cerevisiae and Aspergillus carbonarius were transformed using the LiAc/SS-DNNPEG and Agrobacterium-mediated transformation (AMT), respectively. Surprisingly, increasing ergosterol content did not augment antifungal activity. Furthermore, iturin A's antifungal activity against S. cerevisiae was reduced while it pre-incubation with voltage-gated potassium (Kv) channel inhibitor, indicating that Kv activation was responsible for cell death. Iturin A was found to activate the Kv protein, stimulating K
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