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深入了解甾醇代谢在抗真菌药物耐药性中的作用:一篇综述短文

Insights into the role of sterol metabolism in antifungal drug resistance: a mini-review.

作者信息

Tanwar Sunita, Kalra Sapna, Bari Vinay Kumar

机构信息

Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Bathinda, India.

出版信息

Front Microbiol. 2024 Oct 11;15:1409085. doi: 10.3389/fmicb.2024.1409085. eCollection 2024.

Abstract

Sterols are essential for eukaryotic cells and are crucial in cellular membranes' structure, function, fluidity, permeability, adaptability to environmental stressors, and host-pathogen interactions. Fungal sterol, such as ergosterol metabolism, involves several organelles, including the mitochondria, lipid droplets, endoplasmic reticulum, and peroxisomes that can be regulated mainly by feedback mechanisms and transcriptionally. The majority of sterol transport in yeast occurs via non-vesicular transport pathways mediated by lipid transfer proteins, which determine the quantity of sterol present in the cell membrane. Pathogenic fungi , , and species can cause a range of superficial to potentially fatal systemic and invasive infections that are more common in immunocompromised patients. There is a significant risk of morbidity and mortality from these infections, which are very difficult to cure. Several antifungal drugs with different modes of action have received clinical approval to treat fungal infections. Antifungal drugs targeting the ergosterol biosynthesis pathway are well-known for their antifungal activity; however, an imbalance in the regulation and transport of ergosterol could lead to resistance to antifungal therapy. This study summarizes how fungal sterol metabolism and regulation can modulate sterol-targeting antifungal drug resistance.

摘要

甾醇对真核细胞至关重要,在细胞膜的结构、功能、流动性、通透性、对环境应激源的适应性以及宿主 - 病原体相互作用中起着关键作用。真菌甾醇,如麦角固醇的代谢涉及多个细胞器,包括线粒体、脂滴、内质网和过氧化物酶体,其主要通过反馈机制和转录进行调节。酵母中的大多数甾醇运输是通过由脂质转运蛋白介导的非囊泡运输途径进行的,这些蛋白决定了细胞膜中甾醇的含量。致病性真菌,如 、 和 物种,可引起一系列从浅表到潜在致命的全身和侵袭性感染,在免疫功能低下的患者中更为常见。这些感染存在显著的发病和死亡风险,且极难治愈。几种具有不同作用方式的抗真菌药物已获得临床批准用于治疗真菌感染。靶向麦角固醇生物合成途径的抗真菌药物以其抗真菌活性而闻名;然而,麦角固醇调节和运输的失衡可能导致对抗真菌治疗产生耐药性。本研究总结了真菌甾醇代谢和调节如何调节针对甾醇的抗真菌药物耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a8b/11502366/3c25e35295c1/fmicb-15-1409085-g001.jpg

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