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鞘脂类生物合成途径对 的生长、生物膜形成和膜完整性至关重要。

Sphingolipid biosynthetic pathway is crucial for growth, biofilm formation and membrane integrity of .

机构信息

Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.

Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.

出版信息

Future Med Chem. 2019 Nov;11(22):2905-2917. doi: 10.4155/fmc-2019-0186. Epub 2019 Nov 12.

Abstract

Glycosphingolipids are conserved lipids displaying a variety of functions in fungal cells, such as determination of cell polarity and virulence. They have been considered as potent targets for new antifungal drugs. The present work aimed to test two inhibitors, myriocin and DL-threo-1-Phenyl-2-palmitoylamino-3-morpholino-1-propanol, in , a pathogenic fungus which causes a wide range of disease. Mass spectrometry, microscopy and cell biology approaches showed that treatment with both inhibitors led to defects in fungal growth and membrane integrity, and caused an increased susceptibility to the current antifungal agents. These data demonstrate the antifungal potential of drugs inhibiting sphingolipid biosynthesis, as well as the usefulness of sphingolipids as promising targets for the development of new therapeutic options.

摘要

糖脂是具有多种功能的保守脂质,在真菌细胞中,如确定细胞极性和毒力。它们已被认为是新的抗真菌药物的有效靶点。本研究旨在测试两种抑制剂,即霉菌酸和 DL-threo-1-苯-2-棕榈酰氨基-3-吗啉-1-丙醇,在一种引起广泛疾病的致病真菌中。质谱、显微镜和细胞生物学方法表明,两种抑制剂的处理都会导致真菌生长和膜完整性缺陷,并增加对抗真菌药物的敏感性。这些数据表明抑制鞘脂生物合成的药物具有抗真菌潜力,同时鞘脂作为开发新治疗方法的有前途的靶点具有重要意义。

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