HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence.
HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence.
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DOI：
10.1038/s41598-018-21965-y
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发表时间：
2018-03-26
影响因子：
4.6
通讯作者：
Alspaugh JA
中科院分区：
文献类型：
--
作者：
Brandão F;Esher SK;Ost KS;Pianalto K;Nichols CB;Fernandes L;Bocca AL;Poças-Fonseca MJ;Alspaugh JA
人类真菌病原体新型隐球菌经历许多表型变化，以促进其在特定生态位和宿主内的生存。为了探讨染色质重塑在毒力相关性状表达中的作用，我们在C. neoformans基因组。这些研究表明，单个HDAC控制与毒力相关的不相同但重叠的细胞过程，包括耐热性、荚膜形成、黑色素合成、蛋白酶活性和细胞壁完整性。我们还确定了C.在体外巨噬细胞感染期间和隐球菌病动物模型中的新生菌存活率。我们的研究结果确定了HDA 1 HDAC基因作为一个中央介质控制几个细胞过程，包括交配和毒力。最后，比较hda 1 Δ突变体与野生型的全局基因表达谱显示，与该真菌病原体中最突出的毒力属性相关的特定基因的转录发生了改变。这项研究直接关联的影响，I/II类HDAC介导的染色质重塑显着的表型可塑性和毒力潜力的这种微生物。此外，我们的研究结果提供了有关毒力基因表达的调控机制的见解，这些机制可能与其他微生物病原体共享。
The human fungal pathogen Cryptococcus neoformans undergoes many phenotypic changes to promote its survival in specific ecological niches and inside the host. To explore the role of chromatin remodeling on the expression of virulence-related traits, we identified and deleted seven genes encoding predicted class I/II histone deacetylases (HDACs) in the C. neoformans genome. These studies demonstrated that individual HDACs control non-identical but overlapping cellular processes associated with virulence, including thermotolerance, capsule formation, melanin synthesis, protease activity and cell wall integrity. We also determined the HDAC genes necessary for C. neoformans survival during in vitro macrophage infection and in animal models of cryptococcosis. Our results identified the HDA1 HDAC gene as a central mediator controlling several cellular processes, including mating and virulence. Finally, a global gene expression profile comparing the hda1Δ mutant versus wild-type revealed altered transcription of specific genes associated with the most prominent virulence attributes in this fungal pathogen. This study directly correlates the effects of Class I/II HDAC-mediated chromatin remodeling on the marked phenotypic plasticity and virulence potential of this microorganism. Furthermore, our results provide insights into regulatory mechanisms involved in virulence gene expression that are likely shared with other microbial pathogens.
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