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一种真菌甾醇葡糖苷酶,处于毒力、宿主免疫和治疗开发的交汇点。

A Fungal Sterylglucosidase at the Intersection of Virulence, Host Immunity, and Therapeutic Development.

机构信息

Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.

出版信息

mBio. 2022 Dec 20;13(6):e0242522. doi: 10.1128/mbio.02425-22. Epub 2022 Oct 18.

Abstract

Human fungal infections (mycoses) cause significant morbidity and mortality in high-risk populations. Contemporary antifungal therapies rely heavily on three classes of antifungal drugs, and to date, no fungal vaccine is in clinical use for invasive mycosis. A major gap in knowledge related to fungal vaccine development is identifying lasting mechanisms of protective immunity in immunocompromised individuals. Recent studies in Cryptococcus neoformans and now Aspergillus fumigatus have identified a fungal sterylglucosidase essential for pathogenesis and virulence in murine models of mycoses. Fungal strains deficient in this sterylglucosidase can surprisingly also induce substantial immune-mediated protection against subsequent challenge with wild-type strains in multiple immunocompromised murine models of mycoses. Here, I discuss the implications and future directions of these exciting and impactful results.

摘要

人类真菌感染(真菌病)在高危人群中导致严重的发病率和死亡率。当代抗真菌治疗严重依赖于三类抗真菌药物,迄今为止,尚无真菌疫苗用于侵袭性真菌病。在真菌疫苗开发方面,一个主要的知识空白是确定免疫功能低下个体中持久的保护性免疫机制。最近在新型隐球菌和烟曲霉中的研究发现,真菌甾醇葡糖苷酶对于真菌感染的发病机制和毒力是必需的,在真菌感染的多种免疫功能低下的小鼠模型中,这种甾醇葡糖苷酶可以诱导出显著的免疫介导的保护作用。在这里,我将讨论这些令人兴奋和有影响力的结果的意义和未来方向。

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Aspergillus fumigatus and Aspergillosis in 2019.2019 年烟曲霉和曲霉病。
Clin Microbiol Rev. 2019 Nov 13;33(1). doi: 10.1128/CMR.00140-18. Print 2019 Dec 18.

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