A limited number of antifungal drugs, the side-effect of clinical drugs and the emergence of resistance create an urgent need for new antifungal treatment agents. High-throughput drug screening and in-depth drug action mechanism analyzation are needed to address this problem. In this study, we identified that artemisinin and its derivatives possessed antifungal activity through a high-throughput screening of the FDA-approved drug library. Subsequently, drug-resistant strains construction, a molecular dynamics simulation and a transcription level analysis were used to investigate artemisinin’s action mechanism in Candida glabrata. Transcription factor pleiotropic drug resistance 1 (PDR1) was an important determinant of artemisinin’s sensitivity by regulating the drug efflux pump and ergosterol biosynthesis pathway, leading to mitochondrial dysfunction. This dysfunction was shown by a depolarization of the mitochondrial membrane potential, an enhancement of the mitochondrial membrane viscosity and an upregulation of the intracellular ROS level in fungi. The discovery shed new light on the development of antifungal agents and understanding artemisinin’s action mechanism.
Antioxidants, Free Full-Text, draw it to know it
Antioxidants, Free Full-Text
Mitochondria Circadian Rhythm Flash Sales
Antioxidants, Free Full-Text, renato ruiz pacheco
Antioxidants, Free Full-Text
ONOO--mediated inactivation of HO-1 and HO-2. Rat splee, onoo 2
Antioxidants, Free Full-Text
Antioxidants, Free Full-Text, giro gratis coin master levvvel
Onoo Po Strategies - Onoo Po Strategies, onoo
Antioxidants, Free Full-Text, giro gratis coin master levvvel
Figure 6 from Nitric oxide and peroxynitrite in health and disease., onoo 2 no2
Nitric Oxide Dioxygenase Activity of a Nitrosyl Complex of Mn(II)-Porphyrinate in the Presence of Superoxide: Formation of a Mn(IV)-oxo Species through a Putative Peroxynitrite Intermediate, onoo 2 no2
Antioxidants, Free Full-Text, renato ruiz pacheco
Antioxidants, Free Full-Text, arras io 2000