BSC2 modulates AmB resistance via the maintenance of intracellular sodium/potassium ion homeostasis in Saccharomyces cerevisiae.

IF 2.5 4区生物学 Q3 MICROBIOLOGY

Research in microbiology Pub Date : 2024-09-07 DOI:10.1016/j.resmic.2024.104245

Zhiwei Huang, Fulong Xiao, Qiao Wang, Xiaojuan Zhang, Yuhu Shen, Yunxia Deng, Ping Shi

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引用次数: 0

Abstract

Previous studies on BSC2 have shown that it enhances yeast cell resistance to AmB via antioxidation and induces multidrug resistance by contributing to biofilm formation. Herein, we found that BSC2 overexpression could reverse the sensitivity of pmp3Δ to AmB and help the tested strains restore the intracellular sodium/potassium balance under exposure to AmB. Meanwhile, overexpression of the chitin gene CHS2 could simulate BSC2 to reverse the sensitivity of pmp3Δ and nha1Δ to high salt or AmB. However, BSC2 overexpression in flo11Δ failed to induce AmB resistance, form biofilms, and affect cell wall biogenesis, while CHS2 overexpression compensated the resistance of flo11Δ to AmB. Additionally, BSC2 levels were positively correlated with maintaining cell membrane integrity under exposure to AmB, CAS, or a combination of both. BSC2 overexpression in nha1Δ exhibited a similar function of CHS2, which can compensate for the sensitivity of the mutant to high salt. Altogether, the results demonstrate for the first time that BSC2 may promote ion equilibrium by strengthening cell walls and inhibiting membrane damage in a FLO path-dependent manner, thus enhancing the resistance of yeast cells to AmB. This study also reveals the possible mechanism of antifungal drugs CAS and AmB combined to inhibit fungi.

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BSC2 通过维持酿酒酵母细胞内钠/钾离子平衡调节对 AmB 的抗性

以往对BSC2的研究表明，它能通过抗氧化增强酵母细胞对AmB的抗性，并通过促进生物膜的形成诱导多药抗性。在本文中，我们发现 BSC2 的过表达可以逆转 pmp3Δ 对 AmB 的敏感性，并帮助受试菌株在暴露于 AmB 的情况下恢复细胞内的钠钾平衡。同时，甲壳素基因CHS2的过表达可以模拟BSC2逆转pmp3Δ和nha1Δ对高盐或AmB的敏感性。然而，在flo11Δ中过表达BSC2不能诱导抗AmB、形成生物膜和影响细胞壁的生物生成，而过表达CHS2能补偿flo11Δ对AmB的抗性。此外，BSC2水平与暴露于AmB、CAS或两者结合作用下细胞膜完整性的维持呈正相关。BSC2 在 nha1Δ 中的过表达表现出与 CHS2 类似的功能，可以补偿突变体对高盐的敏感性。总之，研究结果首次证明了BSC2可通过强化细胞壁和抑制膜损伤，以FLO路径依赖的方式促进离子平衡，从而增强酵母细胞对AmB的抗性。这项研究还揭示了抗真菌药物 CAS 和 AmB 联合抑制真菌的可能机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Research in microbiology 生物-微生物学

CiteScore

4.10

自引率

3.80%

发文量

审稿时长

16 days

期刊介绍： Research in Microbiology is the direct descendant of the original Pasteur periodical entitled Annales de l''Institut Pasteur, created in 1887 by Emile Duclaux under the patronage of Louis Pasteur. The Editorial Committee included Chamberland, Grancher, Nocard, Roux and Straus, and the first issue began with Louis Pasteur''s "Lettre sur la Rage" which clearly defines the spirit of the journal:"You have informed me, my dear Duclaux, that you intend to start a monthly collection of articles entitled "Annales de l''Institut Pasteur". You will be rendering a service that will be appreciated by the ever increasing number of young scientists who are attracted to microbiological studies. In your Annales, our laboratory research will of course occupy a central position, but the work from outside groups that you intend to publish will be a source of competitive stimulation for all of us."That first volume included 53 articles as well as critical reviews and book reviews. From that time on, the Annales appeared regularly every month, without interruption, even during the two world wars. Although the journal has undergone many changes over the past 100 years (in the title, the format, the language) reflecting the evolution in scientific publishing, it has consistently maintained the Pasteur tradition by publishing original reports on all aspects of microbiology.