两性霉素B抗真菌作用机制与病原性土曲霉对其耐药机制的研究进展

两性霉素B(amphotericin B, AMB)是经典的多烯类抗真菌药物，对病原真菌具有广谱抗菌活性，且不易产生耐药性。土曲霉是临床上常见的病原性曲霉，因其对AMB天然耐药而受到关注。现阶段，AMB的抗真菌作用机制有待进一步阐明，且真菌对AMB的耐药机制研究亦不充分。本文就AMB在土曲霉中诱导内源性活性氧(reactive oxygen species, ROS)产生的抗真菌作用机制进行介绍，并重点讨论应激适应通路(热休克蛋白90、热休克蛋白70和钙调磷酸酶)、ROS清除酶以及线粒体功能在土曲霉对AMB耐药中的作用。这些新发现对了解AMB在其他病原性曲霉中的作用机制和耐药机制都具有重要的临床意义。

Advances in the study of amphotericin B: mechanisms of antifungal action and resistance mechanisms in pathogenic Aspergillus terreus

Amphotericin B (AMB) is a classical polyene antifungal agent with powerful and broad-spectrum activity against pathogenic fungi, and less likely to be resistant. Aspergillus terreus, a clinically common pathogenic Aspergillus, is gaining attention due to intrinsic AMB resistance. At present, the mode of antifungal action of AMB needs to be further elucidated, and little is known about the mechanism of AMB resistance. This review addresses the novel mode of action by which AMB induces increased endogenous reactive oxygen species (ROS) production in Aspergillus terreus. Also, the role of stress adaptation pathways (heat shock protein 90, heat shock protein 70, and calcineurin), ROS scavenging enzymes, as well as mitochondrial function in the mechanisms of AMB resistance in Aspergillus terreus is highlighted. These novel findings are of great significance in understanding both action and resistance mechanism of AMB in other pathogenic Aspergilli spp. with clinical importance.