Li Yiman, Song Zhihui, Wang Ente, Dong Liming, Bai Jie, Wang Dong, Zhu Jinyan, Zhang Chao
Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Front Microbiol. 2022 Aug 9;13:980615. doi: 10.3389/fmicb.2022.980615. eCollection 2022.
As a primary cause of death in patients with hematological malignancies and transplant recipients, invasive aspergillosis (IA) is a condition that warrants attention. IA infections have been increasing, which remains a significant cause of morbidity and mortality in immunocompromised patients. During the past decade, antifungal drug resistance has emerged, which is especially concerning for management given the limited options for treating azole-resistant infections and the possibility of failure of prophylaxis in those high-risk patients. Histone posttranslational modifications (HPTMs), mainly including acetylation, methylation, ubiquitination and phosphorylation, are crucial epigenetic mechanisms regulating various biological events, which could modify the conformation of histone and influence chromatin-associated nuclear processes to regulate development, cellular responsiveness, and biological phenotype without affecting the underlying genetic sequence. In recent years, fungi have become important model organisms for studying epigenetic regulation. HPTMs involves in growth and development, secondary metabolite biosynthesis and virulence in . This review mainly aims at summarizing the acetylation, deacetylation, methylation, demethylation, and sumoylation of histones in IA and connect this knowledge to possible HPTMs-based antifungal drugs. We hope this research could provide a reference for exploring new drug targets and developing low-toxic and high-efficiency antifungal strategies.
作为血液系统恶性肿瘤患者和移植受者的主要死亡原因，侵袭性曲霉病（IA）是一种值得关注的疾病。IA感染一直在增加，仍然是免疫功能低下患者发病和死亡的重要原因。在过去十年中，出现了抗真菌药物耐药性，鉴于治疗唑类耐药感染的选择有限以及高危患者预防失败的可能性，这一点尤其令人担忧。组蛋白翻译后修饰（HPTMs）主要包括乙酰化、甲基化、泛素化和磷酸化，是调节各种生物学事件的关键表观遗传机制，它可以改变组蛋白的构象并影响与染色质相关的核过程，从而在不影响基础遗传序列的情况下调节发育、细胞反应性和生物学表型。近年来，真菌已成为研究表观遗传调控的重要模式生物。HPTMs参与真菌的生长发育、次级代谢产物生物合成和毒力。本综述主要旨在总结IA中组蛋白的乙酰化、去乙酰化、甲基化、去甲基化和SUMO化，并将这些知识与可能基于HPTM的抗真菌药物联系起来。我们希望这项研究能够为探索新的药物靶点和开发低毒高效的抗真菌策略提供参考。
