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从植物鳞茎中分离出的烟曲霉多个菌株的亲缘关系和杀菌剂抗性。

Intimate genetic relationships and fungicide resistance in multiple strains of Aspergillus fumigatus isolated from a plant bulb.

机构信息

Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8673, Japan.

Molecular Chirality Research Center, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan.

出版信息

Environ Microbiol. 2021 Sep;23(9):5621-5638. doi: 10.1111/1462-2920.15724. Epub 2021 Aug 31.

Abstract

Fungal infections are increasingly dangerous because of environmentally dispersed resistance to antifungal drugs. Azoles are commonly used antifungal drugs, but they are also used as fungicides in agriculture, which may enable enrichment of azole-resistant strains of the human pathogen Aspergillus fumigatus in the environment. Understanding of environmental dissemination and enrichment of genetic variation associated with azole resistance in A. fumigatus is required to suppress resistant strains. Here, we focused on eight strains of azole-resistant A. fumigatus isolated from a single tulip bulb for sale in Japan. This set includes strains with TR /L98H/T289A/I364V/G448S and TR /Y121F/T289A/S363P/I364V/G448S mutations in the cyp51A gene, which showed higher tolerance to several azoles than strains harbouring TR /Y121F/T289A mutation. The strains were typed by microsatellite typing, single nucleotide polymorphism profiles, and mitochondrial and nuclear genome analyses. The strains grouped differently using each typing method, suggesting historical genetic recombination among the strains. Our data also revealed that some strains isolated from the tulip bulb showed tolerance to other classes of fungicides, such as QoI and carbendazim, followed by related amino acid alterations in the target proteins. Considering spatial-temporal factors, plant bulbs are an excellent environmental niche for fungal strains to encounter partners, and to obtain and spread resistance-associated mutations.

摘要

由于环境中抗真菌药物的耐药性扩散,真菌感染变得越来越危险。唑类药物是常用的抗真菌药物,但它们也被用作农业中的杀菌剂,这可能使人类病原体烟曲霉中唑类耐药菌株在环境中富集。为了抑制耐药菌株,需要了解烟曲霉中与唑类耐药相关的遗传变异在环境中的传播和富集。在这里,我们专注于从日本出售的单个郁金香鳞茎中分离出的 8 株唑类耐药烟曲霉。这组包括在 cyp51A 基因中具有 TR/L98H/T289A/I364V/G448S 和 TR/Y121F/T289A/S363P/I364V/G448S 突变的菌株,它们对几种唑类药物的耐受性高于仅具有 TR/Y121F/T289A 突变的菌株。使用微卫星分型、单核苷酸多态性谱以及线粒体和核基因组分析对菌株进行了分型。每种分型方法的菌株分组方式不同,表明菌株之间存在历史遗传重组。我们的数据还表明,从郁金香鳞茎中分离出的一些菌株对其他类别的杀菌剂(如 QoI 和多菌灵)表现出耐受性,随后靶蛋白中出现相关的氨基酸改变。考虑到时空因素,植物鳞茎是真菌菌株遇到伴侣、获得和传播耐药相关突变的绝佳环境小生境。

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