Pócsi I, Sámi L, Leiter E, Majoros L, Szabó B, Emri T, Pusztahelyi T
Department of Microbiology and Biotechnology, Faculty of Sciences, University of Debrecen, P.O. Box 63, H-4010 Debrecen, Hungary.
Acta Microbiol Immunol Hung. 2001;48(3-4):533-43. doi: 10.1556/AMicr.48.2001.3-4.19.
New approaches for treatment of invasive fungal infections are necessary to cope with emerging resistant fungal pathogens of humans. In this paper, three different strategies are presented and evaluated to find new-type antifungal drugs and their targets. While experimental data obtained with potent chitinase inhibitors, e.g. allosamidin, and small-size antifungal proteins of fungal origin are encouraging more efforts are needed to verify and exploit the possible involvement of intracellular thiols, e.g. glutathione, and their metabolic enzymes in the pathogenesis of mycoses caused by dimorphic fungi. Chitinase inhibitors seem to hinder the cell separation of yeasts and the fragmentation of filamentous fungi quite effectively and, hence, they may be implicated in future therapies of systemic mycoses. In addition, small-size antifungal proteins possessing a broad inhibition spectrum may also provide us with promising new agents for the treatment of different kinds of (e.g. cutaneous) fungal infections.
为应对新出现的人类耐药真菌病原体,需要有治疗侵袭性真菌感染的新方法。本文介绍并评估了三种不同策略,以寻找新型抗真菌药物及其靶点。虽然用强效几丁质酶抑制剂(如别洛沙米定)和真菌来源的小尺寸抗真菌蛋白获得的实验数据令人鼓舞,但仍需要更多努力来验证和利用细胞内硫醇(如谷胱甘肽)及其代谢酶在双态真菌引起的真菌病发病机制中的可能作用。几丁质酶抑制剂似乎能非常有效地阻碍酵母细胞分离和丝状真菌碎片化,因此,它们可能会用于未来全身性真菌病的治疗。此外,具有广泛抑制谱的小尺寸抗真菌蛋白也可能为我们提供治疗不同类型(如皮肤)真菌感染的有前景的新药物。