真菌病原体己成为危害人类健康和农业的主要难题。作为一类真核细胞,真菌某些重要的生物特性与哺乳类动物的细胞雷同,以致现有的抗真菌抗生素往往不能区分真菌细胞和哺乳类动物细胞,导致严重的毒副作用。因此急需开发既有效、又安全的新型抗真菌药物。E1族大肠菌素是大肠杆菌产生的一种可形成离子通道的细菌素,它们只能杀伤大肠杆菌及亲缘关系接近的某些细菌。我们应用生物工程技术将白色念珠菌α交配信息素连接在大肠菌素Ia通道结构域上,即构成一种新型融合蛋白——信息菌素一CA(PMC—CA)。间接荧光标记数据显示该信息菌素可结合在真菌细胞上,实验室/田间实验数据证实信息菌素可抑制真菌生长。按分子量标化,田间实验数据证实信息菌素对稻瘟病的保护率显著高于三唑类、三环唑和稻瘟灵等现用抗稻瘟病药物的保护率。上述结果提示该融合蛋白具有发展成为农业抗真菌药物的价值。
Fungal pathogens represent major problems for human health and agriculture. As eukaryotic organisms, fungi share some important features with mammalian cells. Therefore, current anti-fungal antibiotics often can not distinguish between fungi and mam- malian cells, resulting in serious side effects in mammalian cells. Accordingly, there is strong impetus to develop antifungal alterna- tives that are both safe and effective. The E1 family of colicin are channel-forming bacteriocins produced by Escherichia coli, which are bactericidal only to E. coli and related species. To target the channel-forming domain of colicin to fungal cell membrane, we engi- neered a sexual mating pheromone of Candida albicans, a-factor pheromone to colicin Ia. A peptide was constructed consisting of an α mating pheromone of C. albicans fused to the channel-forming domain of colicin Ia to create a new fusion protein, pheromonicin- CA (PMC-CA). Indirect immunolabeling showed that the PMC-CA bound to fungal cells and inhibited growth in the laboratory and field. In the field, the protective activity ofpheromonicin against rice blast disease was significantly greater, on a molar basis, than that of triazoles, tricyclazole or isoprothiolane. These results suggest that fusion peptides may be of value as fungicidal agents under agri- cultural conditions.