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揭开新型隐球菌中卡泊芬净耐药的谜题。

Unraveling Caspofungin Resistance in Cryptococcus neoformans.

机构信息

Host-Pathogen Interaction Study Group (GEIHP, EA 3142), Université Angers, Université Brest, Angers, France

Federative Structure of Research Cellular Interactions and Therapeutic Applications, SFR 4208 ICAT, Université Angers, Angers, France.

出版信息

mBio. 2021 Mar 16;12(2):e00156-21. doi: 10.1128/mBio.00156-21.

Abstract

is a basidiomycetous yeast responsible for hundreds of thousands of deaths a year and is particularly threatening in immunocompromised patients. There are few families of antifungals that are available to fight fungal infections, and the unique efficient treatment for the most deadly cerebral forms of cryptococcosis is based on a combination of 5-fluorocytosine and amphotericin B. The toxicities of both compounds are elevated, and more therapeutic options are urgently needed for better management of life-threatening cryptococcosis. The newest class of antifungals, i.e., echinocandins, has initially led to great hope. Unfortunately, was rapidly confirmed to be naturally resistant to these molecules, notably caspofungin. In this respect, we discuss here the recent key findings of the Panepinto research group published in (M. C. Kalem et al., mBio 12:e03225-20, 2021, https://doi:10.1128/mBio.03225-20) that provide an unprecedented view of how regulates caspofungin resistance through a complex posttranscriptional regulation of cell wall biosynthesis genes.

摘要

是一种担子菌酵母,每年导致数十万人死亡,尤其对免疫功能低下的患者构成威胁。可用于治疗真菌感染的抗真菌药物种类有限,而针对最致命的隐球菌性脑膜炎的独特有效治疗方法基于 5-氟胞嘧啶和两性霉素 B 的联合用药。这两种化合物的毒性都有所增加,迫切需要更多的治疗选择来更好地管理危及生命的隐球菌病。最新一类的抗真菌药物,即棘白菌素类,最初带来了很大的希望。不幸的是,很快就证实 对这些分子,特别是卡泊芬净,具有天然耐药性。在这方面,我们在这里讨论 Panepinto 研究小组最近在 (M. C. Kalem 等人,mBio 12:e03225-20, 2021, https://doi:10.1128/mBio.03225-20)上发表的关键发现,这些发现提供了一个前所未有的视角,展示了 如何通过细胞 壁生物合成基因的复杂转录后调控来调节卡泊芬净耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e2/8092212/02278e030eee/mBio.00156-21-f0001.jpg

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