白念珠菌中 SWI/SNF 染色质重塑复合体对铜吸收的调控影响了在缺氧条件下对抗真菌和氧化应激的敏感性。

IF 2.4 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Inès Khemiri, Faiza Tebbji, Anaïs Burgain, Adnane Sellam
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引用次数: 0

摘要

白色念珠菌是一种人类定植菌,也是一种机会性酵母菌,占据着不同的生境,这些生境大多缺氧。虽然缺氧是宿主体内的普遍状况,但整合氧气状态以调节真菌病原体适应性的机制仍然特征不清。在这里,我们发现染色质重塑复合物 SWI/SNF 的一个亚基 Snf5 是耐受抗真菌胁迫(尤其是在缺氧条件下)所必需的。在缺氧条件下,snf5突变体暴露于两性霉素B和氟康唑的RNA-seq图谱分析发现了一种与铜(Cu)饥饿相似的特征。我们发现,在缺氧和铜饥饿环境下,Snf5对维持铜平衡和铜调节子的转录调控至关重要。此外,Snf5主要在缺氧条件下表现出活性氧水平升高和对氧化应激的敏感性增强。在生长培养基中补充铜或增加铜转运体 CTR1 的基因剂量可减轻 snf5 的生长缺陷,并减轻 ROS 水平对抗真菌挑战的反应。基因相互作用分析表明,Snf5 和真正的铜平衡调节因子 Mac1 在不同的途径中发挥作用。总之,我们的数据强调了 SWI/SNF 复合物在缺氧条件下作为铜代谢和抗真菌胁迫强效调节因子的独特作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Regulation of copper uptake by the SWI/SNF chromatin remodeling complex in Candida albicans affects susceptibility to antifungal and oxidative stresses under hypoxia.

Candida albicans is a human colonizer and also an opportunistic yeast occupying different niches that are mostly hypoxic. While hypoxia is the prevalent condition within the host, the machinery that integrates oxygen status to tune the fitness of fungal pathogens remains poorly characterized. Here, we uncovered that Snf5, a subunit of the chromatin remodeling complex SWI/SNF, is required to tolerate antifungal stress particularly under hypoxia. RNA-seq profiling of snf5 mutant exposed to amphotericin B and fluconazole under hypoxic conditions uncovered a signature that is reminiscent of copper (Cu) starvation. We found that under hypoxic and Cu-starved environments, Snf5 is critical for preserving Cu homeostasis and the transcriptional modulation of the Cu regulon. Furthermore, snf5 exhibits elevated levels of reactive oxygen species and an increased sensitivity to oxidative stress principally under hypoxia. Supplementing growth medium with Cu or increasing gene dosage of the Cu transporter CTR1 alleviated snf5 growth defect and attenuated reactive oxygen species levels in response to antifungal challenge. Genetic interaction analysis suggests that Snf5 and the bona fide Cu homeostasis regulator Mac1 function in separate pathways. Together, our data underlined a unique role of SWI/SNF complex as a potent regulator of Cu metabolism and antifungal stress under hypoxia.

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来源期刊
FEMS yeast research
FEMS yeast research 生物-生物工程与应用微生物
CiteScore
5.70
自引率
6.20%
发文量
54
审稿时长
1 months
期刊介绍: FEMS Yeast Research offers efficient publication of high-quality original Research Articles, Mini-reviews, Letters to the Editor, Perspectives and Commentaries that express current opinions. The journal will select for publication only those manuscripts deemed to be of major relevance to the field and generally will not consider articles that are largely descriptive without insights on underlying mechanism or biology. Submissions on any yeast species are welcome provided they report results within the scope outlined below and are of significance to the yeast field.
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