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组蛋白去乙酰化酶抑制剂可能会降低白色念珠菌的致病性和毒力。

Histone deacetylase inhibitors may reduce pathogenicity and virulence in Candida albicans.

作者信息

Simonetti Giovanna, Passariello Claudio, Rotili Dante, Mai Antonello, Garaci Enrico, Palamara Anna Teresa

机构信息

Department of Public Health Sciences, University of Rome La Sapienza, Rome Italy.

出版信息

FEMS Yeast Res. 2007 Dec;7(8):1371-80. doi: 10.1111/j.1567-1364.2007.00276.x. Epub 2007 Jul 12.

Abstract

Candida albicans is able to establish mucosal and invasive diseases by means of different virulence factors that are frequently regulated by epigenetic mechanisms, including the acetylation-deacetylation of histones and of other regulatory proteins. The focus of our work was on understanding the possible effects of several histone deacetylase inhibitors (HDACi) on the expression of phenotypes that are associated with virulence and pathogenicity in C. albicans, such as adhesion to epithelial cells and the yeast to hypha transition. Some of the HDACi used for experiments caused a 90% reduction in the adherence of C. albicans to human cultured pneumocytes and significantly inhibited serum-induced germination. Inhibition of germination was correlated with a significant reduction in transcription of EFG1. Inhibition appeared less evident when an HDA1-deficient strain was tested. These results suggest that selective and specific HDACi could prove to be a valid approach for selected at-risk patients in the combined treatment of infections caused by C. albicans.

摘要

白色念珠菌能够借助多种毒力因子引发黏膜疾病和侵袭性疾病,这些毒力因子常常受表观遗传机制调控,包括组蛋白及其他调控蛋白的乙酰化-去乙酰化过程。我们工作的重点是了解几种组蛋白脱乙酰酶抑制剂(HDACi)对白色念珠菌中与毒力和致病性相关表型表达的可能影响,如对上皮细胞的黏附以及酵母-菌丝转变。一些用于实验的HDACi使白色念珠菌对人培养肺细胞的黏附减少了90%,并显著抑制血清诱导的萌发。萌发的抑制与EFG1转录的显著减少相关。当测试HDA1缺陷菌株时,抑制作用似乎不太明显。这些结果表明,对于由白色念珠菌引起的感染的联合治疗,选择性和特异性的HDACi可能被证明是针对特定高危患者的有效方法。

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