The emergence of drug-resistant fungi poses a continuously increasing threat to human health. Despite advances in preventive care and diagnostics, resistant fungi continue to cause significant mortality, especially in immunocompromised patients. Therapeutic resources are further limited by current usage of only four major classes of antifungal drugs. Resistance against these drugs has already been observed in pathogenic fungi requiring the development of much needed newer antifungal drugs. Epigenetic changes such as DNA or chromatin modifications alter gene expression levels in response to certain stimuli, including interaction with the host in the case of fungal pathogens. These changes can confer resistance to drugs by altering the expression of target genes or genes encoding drug efflux pumps. Multiple pathogens share many of these epigenetic pathways; thus, targeting epigenetic pathways might also identify drug target candidates for the development of broad-spectrum antifungal drugs. In this review, we discuss the importance of epigenetic pathways in mediating drug resistance in fungi as well as in the development of anti-fungal drugs.

中文翻译：

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真菌耐药性的表观遗传机制。

耐药真菌的出现对人类健康构成了不断增加的威胁。尽管在预防保健和诊断方面取得了进步，但抗药性真菌仍继续导致相当大的死亡率，特别是在免疫功能低下的患者中。目前仅使用四种主要的抗真菌药物进一步限制了治疗资源。已经在致病真菌中观察到对这些药物的抗药性，需要开发急需的新型抗真菌药物。表观遗传变化（例如DNA或染色质修饰）可响应某些刺激（包括在真菌病原体情况下与宿主相互作用）改变基因表达水平。这些改变可以通过改变靶基因或编码药物外排泵的基因的表达来赋予对药物的抗性。多种病原体共享许多这些表观遗传途径。因此，靶向表观遗传途径也可能为广谱抗真菌药物的开发确定候选药物。在这篇综述中，我们讨论了表观遗传途径在介导真菌耐药性以及开发抗真菌药物中的重要性。