Candida albicans requires iron to sustain hyphal growth
Candida albicans requires iron to sustain hyphal growth
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白色念珠菌需要铁来维持菌丝生长
DOI：
10.1016/j.bbrc.2021.05.039
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发表时间：
2021-05-19
影响因子：
3.1
通讯作者：
Lu, Yang
中科院分区：
文献类型：
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作者：
Luo, Gang;Wang, Tianxu;Lu, Yang
白色念珠菌是免疫功能低下个体的一种重要机会性真菌病原体。在酵母和菌丝生长形式之间转换的能力对其致病性至关重要。白色念珠菌的菌丝发育需要两个在时间上相关联的起始和维持调控。在此，我们进行了转录组测序（RNA - Seq）以分析菌丝发育两个不同阶段的转录结果。全基因组转录谱分析显示，与菌丝起始相关的基因集在菌丝细胞壁、生物膜基质和肌动蛋白极化的基因方面显著富集。除了菌丝特异性基因外，许多参与铁摄取的基因，如FTR1和SEF1，在持续的菌丝发育过程中即使在培养基中提供额外的游离铁时也会被特异性地高度诱导。因此，铁摄取基因是由能够以不依赖铁的方式支持菌丝长期发育的信号所诱导。在各种菌丝诱导条件下，通过定量逆转录PCR进一步证实了在菌丝伸长过程中铁摄取基因的诱导。值得注意的是，阻止白色念珠菌摄取铁会阻断BRG1的激活，导致菌丝维持受损，而异位表达的BRG1能够绕过对铁的需求维持菌丝发育。我们的研究阐明了在感染过程中多种毒力因子如何相互关联并同时被诱导的潜在机制。（c）2021爱思唯尔公司。保留所有权利。
Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. The ability to switch between yeast and hyphal growth forms is critical for its pathogenesis. Hyphal development in C. albicans requires two temporally linked regulations for initiation and maintenance. Here, we performed transcriptome sequencing (RNA-Seq) to analyze the transcriptional consequences for the two different phases of hyphal development. Genome-wide transcription profiling reveals that the sets associated with hyphal initiation were significantly enriched in genes for hyphal cell wall, biofilm matrix and actin polarization. In addition to hypha-specific genes, numerous genes involved in iron acquisition, such as FTR1 and SEF1 , are highly induced specifically during sustained hyphal development even when additional free iron is supplied in the medium. Therefore, iron uptake genes are induced by signals that can support prolonged hyphal development in an iron-independent manner. The induction of iron acquisition genes during hyphal elongation was further confirmed by quantitative reverse transcriptionPCR under various hypha-inducing conditions. Remarkably, preventing C. albicans from acquiring iron blocks BRG1 activation, leading to impaired hyphal maintenance, and ectopically expressed BRG1 can sustain hyphal development bypassing the requirement of iron. Our study elucidates an underlying mechanism of how multiple virulence factors are interconnected and are induced simultaneously during infection.(c) 2021 Elsevier Inc. All rights reserved.