纤维素纳米铜粒子的毒性和同化需要麦角菌中的α-停滞蛋白

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Metallomics Pub Date : 2023-03-06 DOI:10.1093/mtomcs/mfad011
Ni Putu Dewi Nurmalasari, Matthew J Winans, Katelyn Perroz, Victoria R Bovard, Robert Anderson, Steve Smith, Jennifer E G Gallagher
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引用次数: 0

摘要

在纳米粒子中越来越多地使用铜等抗菌化合物,改变了活细胞与这些新型材料的相互作用方式。越来越多地使用抗菌纳米材料来防治传染病和食品腐败。真菌感染尤其难以治疗,因为可治疗的靶点很少,而酿酒酵母则为测试这些新材料提供了极具洞察力的模式生物。然而,由于这些材料的新特性,目前还不清楚这些材料如何与活细胞相互作用,也不清楚铜基纳米材料是否会产生抗药性。以含铜的羧甲基纤维素微纤维股(CMC-Cu)为基础的铜纳米颗粒是一种很有前景的纳米材料,当导入酵母细胞后可诱导细胞死亡。α-arrestins是一种货物适配体,可选择将哪些分子导入真核细胞。我们筛选了α-阿司匹林突变体,发现Aly2、Rim8和Rog3 α-阿司匹林是CMC-Cu纳米颗粒内化所必需的。这些突变体的内部活性氧含量较低,这与它们在 CMC-Cu 存在下的存活率提高相对应。利用活细胞晶格光片显微镜,我们确定 CMC-Cu 在暴露 30 分钟内被导入酵母。最初,细胞质 pH 值下降,但 90 分钟后恢复到基本水平。然而,酵母对 CMC-Cu 暴露的反应存在异质性,这可能是由于颗粒的异质性或群体内代谢状态的差异造成的。当酵母暴露于亚致死浓度的 CMC-Cu 时,不会产生抗性。CMC-Cu 的内化提高了这些抗菌纳米材料的效力,可能是防止真菌产生抗药性的关键。
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Toxicity and assimilation of cellulosic copper nanoparticles require α-arrestins in S. cerevisiae.

The increased use of antimicrobial compounds such as copper into nanoparticles changes how living cells interact with these novel materials. The increased use of antimicrobial nanomaterials combats infectious disease and food spoilage. Fungal infections are particularly difficult to treat because of the few druggable targets, and Saccharomyces cerevisiae provides an insightful model organism to test these new materials. However, because of the novel characteristics of these materials, it is unclear how these materials interact with living cells and if resistance to copper-based nanomaterials could occur. Copper nanoparticles built on carboxymethylcellulose microfibril strands with copper (CMC-Cu) are a promising nanomaterial when imported into yeast cells and induce cell death. The α-arrestins are cargo adaptors that select which molecules are imported into eukaryotic cells. We screened α-arrestins mutants and identified Aly2, Rim8, and Rog3 α-arrestins, which are necessary for the internalization of CMC-Cu nanoparticles. Internal reactive oxygen species in these mutants were lower and corresponded to the increased viability in the presence of CMC-Cu. Using lattice light-sheet microscopy on live cells, we determined that CMC-Cu were imported into yeast within 30 min of exposure. Initially, the cytoplasmic pH decreased but returned to basal level 90 min later. However, there was heterogeneity in response to CMC-Cu exposure, which could be due to the heterogeneity of the particles or differences in the metabolic states within the population. When yeast were exposed to sublethal concentrations of CMC-Cu no resistance occurred. Internalization of CMC-Cu increases the potency of these antimicrobial nanomaterials and is likely key to preventing fungi from evolving resistance.

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来源期刊
Metallomics
Metallomics 生物-生化与分子生物学
CiteScore
7.00
自引率
5.90%
发文量
87
审稿时长
1 months
期刊介绍: Global approaches to metals in the biosciences
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