Collaboration between Antagonistic Cell Type Regulators Governs Natural Variation in the Candida albicans Biofilm and Hyphal Gene Expression Network.
Collaboration between Antagonistic Cell Type Regulators Governs Natural Variation in the Candida albicans Biofilm and Hyphal Gene Expression Network.
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DOI：
10.1128/mbio.01937-22
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发表时间：
2022-10-26
期刊：
影响因子：
6.4
通讯作者：
Mitchell, Aaron P.
中科院分区：
文献类型：
--
作者：
Do, Eunsoo;Cravener, Max, V;Huang, Manning Y.;May, Gemma;McManus, C. Joel;Mitchell, Aaron P.
白色念珠菌是人类最重要的真菌病原体之一。然而，绝大多数白色念珠菌的研究都集中在单一的临床分离株及其标记的衍生物上。我们研究了临床分离的白色念珠菌在生物被膜形成的基因调控中的自然变异，这是一个对毒力至关重要的过程。转录因子Efg1是生物膜相关基因表达和生物膜形成所必需的。此前，我们发现Efg1反应基因在5个不同的临床分离株中的表达存在着广泛的差异。然而，染色质免疫沉淀测序分析表明，Efg1与基因组位点的结合在各分离株中是一致的。对菌株差异的功能分析确定了三种转录因子，BRG1、Tec1和Wor1，其表达水平的微小变化重塑了Efg1调控网络。BRG1和Tec1是已知的生物膜激活剂，它们在Efg1网络变异中的作用是可以预期的。然而，Wor1是一种已知的EFG1表达抑制因子和生物膜形成的抑制因子。相反，我们发现WOR1 RNA水平的适度增加，反映了白色念珠菌菌株之间的表达差异，可以促进生物膜的形成和生物膜相关基因的表达。这里对自然变异的分析揭示了一个特征明确的基因的新功能，并说明菌株多样性为阐明网络相互作用提供了独特的资源。
Candida albicans is among the most significant human fungal pathogens. However, the vast majority of C. albicans studies have focused on a single clinical isolate and its marked derivatives. We investigated natural variation among clinical C. albicans isolates in gene regulatory control of biofilm formation, a process crucial to virulence. The transcription factor Efg1 is required for biofilm-associated gene expression and biofilm formation. Previously, we found extensive variation in Efg1-responsive gene expression among 5 diverse clinical isolates. However, chromatin immunoprecipitation sequencing analysis showed that Efg1 binding to genomic loci was uniform among the isolates. Functional dissection of strain differences identified three transcription factors, Brg1, Tec1, and Wor1, for which small changes in expression levels reshaped the Efg1 regulatory network. Brg1 and Tec1 are known biofilm activators, and their role in Efg1 network variation may be expected. However, Wor1 is a known repressor of EFG1 expression and an inhibitor of biofilm formation. In contrast, we found that a modest increase in WOR1 RNA levels, reflecting the expression differences between C. albicans strains, could augment biofilm formation and expression of biofilm-related genes. The analysis of natural variation here reveals a novel function for a well-characterized gene and illustrates that strain diversity offers a unique resource for elucidation of network interactions.
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影响因子：
3.7
作者：
Gustafsson J;Held F;Robinson JL;Björnson E;Jörnsten R;Nielsen J
通讯作者：
Nielsen J
影响因子：
0.8
作者：
Cravener, Max, V;Mitchell, Aaron P.
通讯作者：
Mitchell, Aaron P.
影响因子：
5.7
作者：
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影响因子：
4.5
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通讯作者：
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DOI：
10.1038/nrmicro.2017.107
发表时间：
2018-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Lohse MB;Gulati M;Johnson AD;Nobile CJ
通讯作者：
Nobile CJ