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组蛋白乙酰转移酶抑制剂 (HATi) 与槲皮素协同抑制热带假丝酵母生物膜的形成。

Synergy of histone acetyltransferase inhibitor (HATi) with quercetin inhibits biofilm formation in Candida tropicalis.

机构信息

Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603203 Tamil Nadu, India.

School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea.

出版信息

Lett Appl Microbiol. 2024 Sep 2;77(9). doi: 10.1093/lambio/ovae085.

Abstract

Histone acetyltransferase inhibitors (HATi) are mechanism-based inhibitors that show promise in the treatment of several illnesses, including diabetes, hyperlipidemia, cancer, and Alzheimer's disease. The work emphasizes the significance of HATi as a possible treatment strategy against Candida species biofilms. Here, in this study, we found that combining a HATi, anacardic acid (AA), and quercetin, a known flavonoid, significantly prevented biofilm formation by C. tropicalis. We further show that C. tropicalis exhibited a considerable downregulation of drug-resistance gene expression (CDR1 and MDR1) when co-administrated. Additionally, in silico studies revealed that the AA interacts strongly with a histone acetyltransferase, Rtt109, which may account for the observed biofilm inhibitory effect. In conclusion, the study illustrates how HATi may be used to potentiate the inhibitory action of phytoactives or antifungals against drug-resistant yeast infections.

摘要

组蛋白乙酰转移酶抑制剂 (HATi) 是一种基于机制的抑制剂,在治疗包括糖尿病、高血脂、癌症和阿尔茨海默病在内的多种疾病方面显示出巨大潜力。这项工作强调了 HATi 作为一种可能的治疗策略来对抗念珠菌生物膜的重要性。在本研究中,我们发现 HATi 漆酚酸(AA)与众所周知的黄酮类化合物槲皮素联合使用,可显著抑制热带念珠菌的生物膜形成。我们进一步表明,当联合使用时,热带念珠菌的耐药基因表达(CDR1 和 MDR1)明显下调。此外,计算机模拟研究表明,AA 与组蛋白乙酰转移酶 Rtt109 强烈相互作用,这可能是观察到的生物膜抑制作用的原因。总之,该研究说明了 HATi 如何可用于增强植物活性物质或抗真菌药物对耐药性酵母感染的抑制作用。

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