College of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China.
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
Sci Rep. 2017 May 16;7(1):1967. doi: 10.1038/s41598-017-01452-6.
The environmentally friendly antibiotic phenazine-1-carboxylic acid (PCA) protects plants, mammals and humans effectively against various fungal pathogens. However, the mechanism by which PCA inhibits or kills fungal pathogens is not fully understood. We analyzed the effects of PCA on the growth of two fungal model organisms, Saccharomyces cerevisiae and Candida albicans, and found that PCA inhibited yeast growth in a dose-dependent manner which was inversely dependent on pH. In contrast, the commonly used antibiotic hygromycin B acted in a dose-dependent manner as pH increased. We then screened a yeast mutant library to identify genes whose mutation or deletion conferred resistance or sensitivity to PCA. We isolated 193 PCA-resistant or PCA-sensitive mutants in clusters, including vesicle-trafficking- and autophagy-defective mutants. Further analysis showed that unlike hygromycin B, PCA significantly altered intracellular vesicular trafficking under growth conditions and blocked autophagy under starvation conditions. These results suggest that PCA inhibits or kills pathogenic fungi in a complex way, in part by disrupting vesicular trafficking and autophagy.
环保型抗生素吩嗪-1-羧酸（PCA）可有效保护植物、哺乳动物和人类免受各种真菌病原体的侵害。然而，PCA 抑制或杀死真菌病原体的机制尚未完全阐明。我们分析了 PCA 对两种真菌模式生物酿酒酵母和白色念珠菌生长的影响，发现 PCA 以剂量依赖的方式抑制酵母生长，且这种抑制作用与 pH 值呈反比。相比之下，常用抗生素 Hygromycin B 则随着 pH 值的升高以剂量依赖的方式发挥作用。然后，我们筛选了酵母突变体文库，以鉴定那些基因突变或缺失赋予 PCA 抗性或敏感性的基因。我们分离到了 193 个 PCA 抗性或 PCA 敏感性突变体，这些突变体聚类在一起，包括囊泡运输和自噬缺陷突变体。进一步的分析表明，与 Hygromycin B 不同，PCA 在生长条件下显著改变了细胞内囊泡运输，并且在饥饿条件下阻断了自噬。这些结果表明，PCA 通过破坏囊泡运输和自噬，以复杂的方式抑制或杀死致病真菌。
