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西奈芬净是S-腺苷甲硫氨酸的一种天然核苷类似物，会损害……的致病性。 （原文此处不完整）

Sinefungin, a natural nucleoside analog of S-adenosyl methionine, impairs the pathogenicity of .

作者信息

Nayak Anushka, Khedri Azam, Chavarria Alejandro, Sanders Kyla N, Ghalei Homa, Khoshnevis Sohail

机构信息

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.

出版信息

NPJ Antimicrob Resist. 2024;2(1). doi: 10.1038/s44259-024-00040-9. Epub 2024 Sep 2.

DOI:10.1038/s44259-024-00040-9
PMID:39268078
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11391927/
Abstract

, an opportunistic fungal pathogen, causes life-threatening infections in immunocompromised patients. Current antifungals are limited by toxicity, drug-drug interactions, and emerging resistance, underscoring the importance of identifying novel treatment approaches. Here, we elucidate the impact of sinefungin, an analog of S-adenosyl methionine, on the virulence of strain SC5314 and clinical isolates. Our data indicate that sinefungin impairs pathogenic traits of including hyphal morphogenesis, biofilm formation, adhesion to epithelial cells, and virulence towards , highlighting sinefungin as an avenue for therapeutic intervention. We determine that sinefungin particularly disturbs N6-methyladenosine (mA) formation. Transcriptome analysis of hyphae upon sinefungin treatment reveals an increase in transcripts related to the yeast form and decrease in those associated with hyphae formation and virulence. Collectively, our data propose sinefungin as a potent molecule against and emphasize further exploration of post-transcriptional control mechanisms of pathogenicity for antifungal design.

摘要

作为一种机会性真菌病原体，在免疫功能低下的患者中会引发危及生命的感染。目前的抗真菌药物受到毒性、药物相互作用以及新出现的耐药性的限制，这凸显了寻找新治疗方法的重要性。在此，我们阐明了S-腺苷甲硫氨酸类似物西奈芬净对菌株SC5314和临床分离株毒力的影响。我们的数据表明，西奈芬净损害了该菌的致病特性，包括菌丝形态发生、生物膜形成、对上皮细胞的粘附以及对小鼠的毒力，突出了西奈芬净作为一种治疗干预途径的潜力。我们确定西奈芬净特别干扰N6-甲基腺苷（m6A）的形成。对经西奈芬净处理的该菌菌丝进行转录组分析发现，与酵母形态相关的转录本增加，而与菌丝形成和毒力相关的转录本减少。总体而言，我们的数据表明西奈芬净是一种对抗该菌的有效分子，并强调进一步探索致病性的转录后调控机制以用于抗真菌药物设计。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75b7/11721669/482f90d8c7ef/44259_2024_40_Fig9_HTML.jpg
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