Transcriptional response of Candida albicans to nitric oxide and the role of the YHB1 gene in nitrosative stress and virulence
Transcriptional response of Candida albicans to nitric oxide and the role of the YHB1 gene in nitrosative stress and virulence
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DOI：
10.1091/mbc.e05-05-0435
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发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Johnson, AD
中科院分区：
文献类型：
--
作者：
Hromatka, BS;Noble, SM;Johnson, AD
在这里，我们研究了白色念珠菌（最常见的人类真菌病原体）如何保护自身免受一氧化氮（（NO）-N-中心点）（一种由先天免疫系统产生的抗菌化合物）的侵害。我们表明，通过全基因组微阵列分析确定，白色念珠菌暴露于（NO）-N-中心点会引发可重复且特异性的转录反应。许多基因被 (NO)-N-中心点短暂诱导或抑制，而一组九个基因在 (NO)-N-中心点暴露期间保持升高水平。后一类中诱导程度最高的基因是 YHB1，这是一种黄素血红蛋白，可以解毒白色念珠菌和其他微生物中的 (NO)-N-中心点。我们发现，YHB1 缺失的白色念珠菌菌株在体外有两种表型；它们对（NO）-N-中心点高度敏感，并且它们是超丝状的。在播散性念珠菌病小鼠模型中，YHB1 缺失的白色念珠菌菌株显示出适度减弱的毒力，但宿主 NOS2 基因的缺失并不能抑制毒力缺陷。这些结果表明，(NO)-N-中心点的产生并不是念珠菌病小鼠尾静脉模型中毒力的主要决定因素，并且yhb1 Delta/yhb1 Delta菌株的毒力减弱可归因于除(NO)-N-中心点解毒能力降低之外的缺陷。
Here, we investigate how Candida albicans, the most prevalent human fungal pathogen, protects itself from nitric oxide ((NO)-N-center dot), an antimicrobial compound produced by the innate immune system. We show that exposure of C. albicans to (NO)-N-center dot elicits a reproducible and specific transcriptional response as determined by genome-wide microarray analysis. Many genes are transiently induced or repressed by (NO)-N-center dot, whereas a set of nine genes remain at elevated levels during (NO)-N-center dot exposure. The most highly induced gene in this latter category is YHB1, a flavohemoglobin that detoxifies (NO)-N-center dot in C. albicans and other microbes. We show that C. albicans strains deleted for YHB1 have two phenotypes in vitro; they are hypersensitive to (NO)-N-center dot and they are hyperfilamentous. In a mouse model of disseminated candidiasis, a YHB1 deleted C. albicans strain shows moderately attenuated virulence, but the virulence defect is not suppressed by deletion of the host NOS2 gene. These results suggest that (NO)-N-center dot production is not a prime determinant of virulence in the mouse tail vein model of candidiasis and that the attenuated virulence of a yhb1 Delta/yhb1 Delta strain is attributable to a defect other than its reduced ability to detoxify (NO)-N-center dot.