Efflux in fungi: la pièce de résistance.

Efflux in fungi: la pièce de résistance.
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DOI:
10.1371/journal.ppat.1000486
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发表时间:
2009-06
期刊:
影响因子:
6.7
通讯作者:
Mylonakis E
Mylonakis E
中科院分区:
医学1区
文献类型:
--
作者:
Coleman JJ;Mylonakis E

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病原体必须能够克服宿主防御和抗微生物治疗,以便成功感染并维持宿主的定殖。真菌完成这一壮举并克服细胞间毒素积累的一种方式是外排泵,特别是ATP结合盒转运蛋白和主要易化剂超家族的转运蛋白。这两个超家族的成员通过分别与ATP水解或质子梯度耦合转运来去除许多有毒化合物。与其他生物体相比,真菌基因组编码这些转运蛋白家族的过多成员。在这篇综述中,我们讨论了这两个真菌超家族的转运蛋白在毒力和抗真菌药物抗性中的作用。这些外排转运蛋白不仅负责参与发病机制的化合物(如次级代谢产物)的输出,还负责宿主衍生的抗菌化合物的输出。此外,我们研究了目前的知识,这些转运蛋白的耐药病原体临床相关的抗真菌药物。
Pathogens must be able to overcome both host defenses and antimicrobial treatment in order to successfully infect and maintain colonization of the host. One way fungi accomplish this feat and overcome intercellular toxin accumulation is efflux pumps, in particular ATP-binding cassette transporters and transporters of the major facilitator superfamily. Members of these two superfamilies remove many toxic compounds by coupling transport with ATP hydrolysis or a proton gradient, respectively. Fungal genomes encode a plethora of members of these families of transporters compared to other organisms. In this review we discuss the role these two fungal superfamilies of transporters play in virulence and resistance to antifungal agents. These efflux transporters are responsible not only for export of compounds involved in pathogenesis such as secondary metabolites, but also export of host-derived antimicrobial compounds. In addition, we examine the current knowledge of these transporters in resistance of pathogens to clinically relevant antifungal agents.
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