Histone Deacetylases and Their Inhibition in Candida Species.
Histone Deacetylases and Their Inhibition in Candida Species.
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组蛋白脱乙酰基酶及其在念珠菌中的抑制作用。
DOI：
10.3389/fmicb.2016.01238
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发表时间：
2016
影响因子：
5.2
通讯作者：
Govin J
中科院分区：
文献类型：
--
作者：
Garnaud C;Champleboux M;Maubon D;Cornet M;Govin J
真菌通常是人类粘膜植物群的良性成员，或者作为寄生虫生活在环境中。然而，它们可能成为致病性的，导致脆弱患者的侵入性和危及生命的感染。这些侵袭性真菌感染被认为是一个重大的公共卫生问题，其规模与结核病或疟疾相似。目前对这些感染的治疗仅基于四种可用的药物类别。这种有限的治疗手段和耐药菌株的出现是一个令人担忧的问题，因为需要治疗的患者越来越多，迫切需要新的治疗策略。真菌对药物压力的适应涉及转录调控，其中染色质动力学和组蛋白修饰起主要作用。组蛋白脱乙酰基酶（HDAC）从组蛋白去除乙酰基并积极参与控制应激反应。HDAC抑制已显示限制真菌发育、毒力、生物膜形成和在感染宿主中的传播，同时还改善现有抗真菌药物对念珠菌属的功效。本文综述了HDAC的功能作用以及HDAC抑制剂对念珠菌的生物学效应，突出了它们在体外和体内的致病作用之间的相关性。我们专注于如何HDAC抑制剂可用于治疗侵袭性念珠菌病，同时也回顾了其临床评价的最新进展。
Fungi are generally benign members of the human mucosal flora or live as saprophytes in the environment. However, they can become pathogenic, leading to invasive and life threatening infections in vulnerable patients. These invasive fungal infections are regarded as a major public health problem on a similar scale to tuberculosis or malaria. Current treatment for these infections is based on only four available drug classes. This limited therapeutic arsenal and the emergence of drug-resistant strains are a matter of concern due to the growing number of patients to be treated, and new therapeutic strategies are urgently needed. Adaptation of fungi to drug pressure involves transcriptional regulation, in which chromatin dynamics and histone modifications play a major role. Histone deacetylases (HDACs) remove acetyl groups from histones and actively participate in controlling stress responses. HDAC inhibition has been shown to limit fungal development, virulence, biofilm formation, and dissemination in the infected host, while also improving the efficacy of existing antifungal drugs toward Candida spp. In this article, we review the functional roles of HDACs and the biological effects of HDAC inhibitors on Candida spp., highlighting the correlations between their pathogenic effects in vitro and in vivo. We focus on how HDAC inhibitors could be used to treat invasive candidiasis while also reviewing recent developments in their clinical evaluation.