Post-transcriptional control of antifungal resistance in human fungal pathogens.
Post-transcriptional control of antifungal resistance in human fungal pathogens.
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人类真菌病原体抗真菌耐药性的转录后控制。
DOI：
10.1080/1040841x.2022.2080527
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发表时间：
2023
影响因子：
6.5
通讯作者：
Kadosh,David
中科院分区：
文献类型：
--
作者：
Sharma,Cheshta;Kadosh,David
全球估计表明，每年有超过3亿各年龄段的人受到严重真菌感染的影响，最终导致约170万人死亡。由于机会性真菌病原体对公共卫生部门造成的社会和经济负担相当大，特别是在免疫功能低下的患者中。尽管这些感染性病原体的临床意义很高，但治疗选择有限，只有三种主要类别的抗真菌药物被批准使用。真菌性疾病的临床管理进一步受到抗真菌药耐药菌株的出现的影响。控制人类真菌病原体耐药性的转录和遗传机制已得到充分研究，包括药物靶标改变、药物外排泵上调以及靶蛋白的药物亲和力和丰度变化。在这篇综述中，我们强调了几个最近发现的新的转录后机制，控制抗真菌药物耐药性，其中涉及在翻译，翻译后，表观遗传和mRNA稳定性水平的调节。许多这些新机制的发现为开发更有效的抗真菌治疗策略开辟了新的途径，并讨论了促进这一过程的新见解，观点和未来方向。
Global estimates suggest that over 300 million individuals of all ages are affected by serious fungal infections every year, culminating in about 1.7 million deaths. The societal and economic burden on the public health sector due to opportunistic fungal pathogens is quite significant, especially among immunocompromised patients. Despite the high clinical significance of these infectious agents, treatment options are limited with only three major classes of antifungal drugs approved for use. Clinical management of fungal diseases is further compromised by the emergence of antifungal resistant strains. Transcriptional and genetic mechanisms that control drug resistance in human fungal pathogens are well-studied and include drug target alteration, upregulation of drug efflux pumps as well as changes in drug affinity and abundance of target proteins. In this review, we highlight several recently discovered novel post-transcriptional mechanisms that control antifungal resistance, which involve regulation at the translational, post-translational, epigenetic, and mRNA stability levels. The discovery of many of these novel mechanisms has opened new avenues for the development of more effective antifungal treatment strategies and new insights, perspectives, and future directions that will facilitate this process are discussed.