PDF(Pubmed)
Abstract：
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.
摘要：
白色念珠菌是一种人类定殖者，也是一种机会性酵母，占据了大多数缺氧的不同生态位。虽然缺氧是宿主体内普遍存在的情况，整合氧气状态以调整真菌病原体适应性的机器仍然缺乏特征。这里,我们发现，Snf5，染色质重塑复合物SWI/SNF的一个亚基，需要耐受抗真菌应激，特别是在缺氧下。在低氧条件下暴露于两性霉素B和氟康唑的snf5突变体的RNA-seq分析揭示了一个让人联想到铜（Cu）饥饿的特征。我们发现在缺氧和铜匮乏的环境下，Snf5对于保持Cu稳态和Cu调节子的转录调节至关重要。此外，snf5主要在缺氧下表现出升高的活性氧水平和对氧化应激的敏感性增加。用Cu补充生长培养基或增加铜转运蛋白CTR1的基因剂量减轻了snf5生长缺陷并降低了ROS水平，以响应抗真菌攻击。遗传相互作用分析表明，Snf5和真正的Cu稳态调节剂Mac1在不同的途径中起作用。一起,我们的数据强调了SWI/SNF复合物作为低氧条件下铜代谢和抗真菌应激的有效调节因子的独特作用.
