La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
Cell Mol Life Sci. 2014 Jul;71(14):2651-66. doi: 10.1007/s00018-014-1573-8. Epub 2014 Feb 14.
Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.
真菌疾病是农业和人类健康中日益严重的问题。人类真菌感染的治疗涉及使用化学杀真菌剂，这些杀真菌剂通常针对真菌质膜或细胞壁的完整性。用于治疗植物病害的化学杀真菌剂具有更多不同的作用机制，包括抑制固醇生物合成、微管组装和线粒体呼吸链。然而，这些治疗方法存在局限性，包括毒性和耐药性的出现。这导致人们越来越关注使用抗菌肽来治疗植物和人类的真菌感染。抗菌肽是一组具有不同作用机制的多样化分子，其中许多分子的作用机制仍知之甚少。此外，越来越明显的是，应激反应途径参与了真菌对化学杀真菌剂和抗菌肽的耐受性。这些信号通路，如细胞壁完整性和高渗甘油途径，是由细胞壁不稳定、渗透压变化和活性氧产生等刺激触发的。在这里，我们综述了用化学杀真菌剂和抗真菌肽处理真菌所诱导的应激信号。这些途径的研究不仅深入了解了这些分子如何发挥其抗真菌作用，还深入了解了真菌耐受这些分子亚致死处理的机制。失活应激反应途径代表了提高抗真菌分子疗效的一种潜在方法。
