Coleman Jeffrey J, Mylonakis Eleftherios
Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS Pathog. 2009 Jun;5(6):e1000486. doi: 10.1371/journal.ppat.1000486. Epub 2009 Jun 26.
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.
病原体必须能够克服宿主防御和抗菌治疗，才能成功感染宿主并维持在宿主体内的定植。真菌实现这一壮举并克服细胞内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子超家族的转运蛋白。这两个超家族的成员分别通过将转运与ATP水解或质子梯度偶联来清除许多有毒化合物。与其他生物相比，真菌基因组编码了大量这些转运蛋白家族的成员。在这篇综述中，我们讨论了这两个真菌转运蛋白超家族在毒力和抗真菌药物耐药性中所起的作用。这些外排转运蛋白不仅负责输出参与发病机制的化合物，如次生代谢产物，还负责输出宿主来源的抗菌化合物。此外，我们研究了目前关于这些转运蛋白在病原体对临床相关抗真菌药物耐药性方面的知识。
