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致病真菌多药耐药性的调控。

Regulation of multidrug resistance in pathogenic fungi.

机构信息

Institut für Molekulare Infektionsbiologie, Universität Würzburg, Röntgenring 11, D-97070 Würzburg, Germany.

出版信息

Fungal Genet Biol. 2010 Feb;47(2):94-106. doi: 10.1016/j.fgb.2009.08.002. Epub 2009 Aug 7.

Abstract

Infections by opportunistic pathogenic fungi, especially Candida species, Cryptococcus neoformans, and Aspergillus fumigatus, are a serious medical problem in immunocompromised patients. Different classes of antimycotic drugs are available to treat fungal infections, but the pathogens can develop resistance to all these agents. A major mechanism of antifungal drug resistance is the overexpression of efflux pumps of the ABC transporter and major facilitator superfamilies, which confer resistance to many structurally and functionally unrelated toxic compounds. For some pathogenic fungi, like Candida albicans and Candida glabrata, the most important drug transporters, transcription factors controlling their expression, and mutations that cause the constitutive upregulation of the efflux pumps in drug-resistant clinical isolates have been identified. For other important pathogens comparatively little is known about the role of transporters in antimycotic resistance. This review summarizes our current knowledge about efflux pump-mediated drug resistance and its regulation in human-pathogenic fungi.

摘要

机会致病性真菌(尤其是念珠菌属、新生隐球菌和烟曲霉)的感染是免疫功能低下患者的严重医学问题。有不同类别的抗真菌药物可用于治疗真菌感染,但病原体可能对所有这些药物产生耐药性。抗真菌药物耐药性的一个主要机制是 ABC 转运蛋白和主要易化因子超家族的外排泵过度表达,这使它们对许多结构和功能上无关的有毒化合物产生耐药性。对于一些病原真菌,如白色念珠菌和光滑念珠菌,已经确定了最重要的药物转运蛋白、控制其表达的转录因子,以及导致耐药临床分离株中外排泵组成性上调的突变。对于其他重要的病原体,关于转运蛋白在抗真菌耐药性中的作用知之甚少。这篇综述总结了我们目前对抗真菌药物耐药性及其在人类病原真菌中的调节机制的了解。

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