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2,4-二乙酰基间苯三酚调节毒力。

2,4-Diacetylphloroglucinol Modulates Virulence.

作者信息

Stepanov Artyom A, Poshvina Darya V, Vasilchenko Alexey S

机构信息

Laboratory of Antimicrobial Resistance, Institute of Environmental and Agricultural Biology (X-BIO), Tyumen State University, Volodarskogo Street, 6, 625003 Tyumen, Russia.

出版信息

J Fungi (Basel). 2022 Sep 27;8(10):1018. doi: 10.3390/jof8101018.

Abstract

The dimorphic fungus is one of the most important opportunistic pathogens for humankind. The use of fungicides against could be associated with sub-inhibitory effects, which are referred to as fungal stress responses and are undesirable for the host. In this work, we investigated the antifungal action of 2,4-diacetylphloroglucinol (2,4-DAPG) against ATCC 10231 with a focus on their biofilm-forming ability. We found that 2,4-DAPG was able to reduce the ability of cells to form biofilms, but complete inhibition and eradication effects were not achieved. Furthermore, cells in the adherent state were characterized by reduced susceptibility to 2,4-DAPG compared to planktonic cells. The investigation of the mechanisms that could explain the antibiofilm action of 2,4-DAPG revealed a reduction in the cell`s surface hydrophobicity and the inhibition of the yeast-to-hyphae transition. The inhibition of the cells filamentation was accompanied by an increase in the expression of the gene, which is a negative regulator of hyphal development. In addition, we microscopically visualized the treated biofilms and revealed numerous channels that were decorated with particles and localized on the hyphae. We assumed that these hyphal structures could be associated with the secretion of aspartyl proteases (Sap). The performed assessments revealed an increase in the activity of Sap, which was accompanied by an increase in the expression of the and genes. The antifungal action of 2,4-DAPG is known to be associated with affecting the permeability of cellular structures, which leads to HATPase malfunction and the disruption of mitochondrial respiration. The subsequent cytosol acidification and generation of ROS trigger the inhibition of filamentation and activation of Sap production. The introduction of antioxidant Trolox simultaneously with 2,4-DAPG leads to a reduction in Sap production. Collectively, the obtained data indicate new aspects of the interaction of fungal cells with 2,4-DAPG, an antimicrobial metabolite of spp.

摘要

双态真菌是人类最重要的机会性病原菌之一。使用杀真菌剂对抗该真菌可能会产生亚抑制效应,这种效应被称为真菌应激反应,对宿主不利。在这项工作中,我们研究了2,4 - 二乙酰基间苯三酚(2,4 - DAPG)对烟曲霉ATCC 10231的抗真菌作用,重点关注其形成生物膜的能力。我们发现2,4 - DAPG能够降低烟曲霉细胞形成生物膜的能力,但未实现完全抑制和根除效果。此外,与浮游细胞相比,处于附着状态的烟曲霉细胞对2,4 - DAPG具有较低的敏感性。对可解释2,4 - DAPG抗生物膜作用机制的研究表明,细胞表面疏水性降低以及酵母 - 菌丝转变受到抑制。烟曲霉细胞丝状化的抑制伴随着brlA基因表达的增加,brlA基因是菌丝发育的负调节因子。此外,我们通过显微镜观察了经处理的生物膜,发现了许多装饰有颗粒并位于菌丝上的通道。我们推测这些菌丝结构可能与天冬氨酸蛋白酶(Sap)的分泌有关。所进行的评估显示Sap活性增加,同时伴随着sppA和sppB基因表达的增加。已知2,4 - DAPG的抗真菌作用与影响细胞结构的通透性有关,这会导致HATPase功能障碍和线粒体呼吸的破坏。随后的胞质溶胶酸化和活性氧的产生触发了烟曲霉丝状化的抑制和Sap产生的激活。与2,4 - DAPG同时引入抗氧化剂Trolox会导致Sap产生减少。总体而言,所获得的数据揭示了真菌细胞与2,4 - DAPG(一种绿针假单胞菌属的抗菌代谢产物)相互作用的新方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d83/9604888/dc66eca1cf56/jof-08-01018-g001.jpg

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