曲霉菌对唑类抗真菌药物的耐药机制研究进展

Research progress on the mechanism of Aspergillus fungi resistant to azoles family antifugal agents

侵袭性曲霉病是由致病曲霉菌引起的危及生命的真菌感染,主要致病菌为烟曲霉,而唑类抗真菌药物是临床治疗的首选。目前已上市的唑类抗真菌药物包括伊曲康唑,伏立康唑,泊沙康唑和伊沙康唑。然而,流行病学研究发现曲霉菌对唑类抗真菌药物的耐药率呈逐年上升趋势,给临床治疗造成了威胁。其中,Cyp51A蛋白突变、外排系统高表达以及环境耐药机制等多种因素都参与唑类抗真菌药物的耐药。因此,本文综述近年来有关曲霉菌对唑类抗真菌药物的耐药机制,以期为耐药监测、耐药菌控制和新药研发提供理论依据。

Invasive aspergillosis is a life-threatening mycosis caused by the pathogenic fungus Aspergillus, especially Aspergillus fumigatus. Azole drugs are the treatment of first choice, including itraconazole, voriconazole, posaconazole, and isavuconazole. However, drug resistance monitoring data show that the azole-resistant Aspergillus fungi rate has increased significantly and posed a threat to clinical treatment. The resistance mechanisms include CYP51 protein mutations, overexpression of efflux transporters, and environmentally-derived resistance mechanisms. Here the studies on the resistance mechanisms of Aspergillus fungi resistant to azole are reviewed, in order to provide the theoretical basis for resistance surveillance, control, and drug discovery.