Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, No. 29, Zhongguancun East Road, Beijing, 100190, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Adv Healthc Mater. 2024 Jul;13(17):e2303755. doi: 10.1002/adhm.202303755. Epub 2024 Mar 9.
Short-chain antifungal peptides (AFPs) inspired by histatin 5 have been designed to address the problem of antifungal drug resistance. These AFPs demonstrate remarkable antifungal activity, with a minimal inhibitory concentration as low as 2 µg mL. Notably, these AFPs display a strong preference for targeting fungi rather than bacteria and mammalian cells. This is achieved by binding the histidine-rich domains of the AFPs to the Ssa1/2 proteins in the fungal cell wall, as well as the reduced membrane-disrupting activity due to their low amphiphilicity. These peptides disrupt the nucleus and mitochondria once inside the cells, leading to reactive oxygen species production and cell damage. In a mouse model of vulvovaginal candidiasis, the AFPs demonstrate not only antifungal activity, but also promote the growth of beneficial Lactobacillus spp. This research provides valuable insights for the development of fungus-specific AFPs and offers a promising strategy for the treatment of fungal infectious diseases.
受组蛋白 5 启发设计的短链抗真菌肽（AFPs）旨在解决抗真菌药物耐药性的问题。这些 AFP 表现出显著的抗真菌活性，最低抑菌浓度低至 2µg/mL。值得注意的是，这些 AFP 表现出强烈的靶向真菌而非细菌和哺乳动物细胞的偏好。这是通过将 AFP 中的富含组氨酸的结构域与真菌细胞壁中的 Ssa1/2 蛋白结合，以及由于其低两亲性而降低的膜破坏活性来实现的。这些肽一旦进入细胞，就会破坏细胞核和线粒体，导致活性氧的产生和细胞损伤。在阴道念珠菌病的小鼠模型中，AFPs 不仅表现出抗真菌活性，还促进有益的乳杆菌属的生长。这项研究为真菌特异性 AFP 的开发提供了有价值的见解，并为治疗真菌感染性疾病提供了有前途的策略。
