Biological consequences and mechanistic mechanisms of mitochondrial dysfunction induced by BMVC-12C-P in Candida albicans

• Main Authors: Man Shen, 沈縵
• Other Authors: Chin-Tin Chen
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/j57ab2

博士 === 國立臺灣大學 === 生化科技學系 === 107 === Candida species are important pathogens causing nosocomial infections and the prob-lem of antifungal drugs resistance in clinical is also a serious problem. At present, we do not have many choices for antifungal agents to use so it is necessary and urgent to develop new antifungal drugs. In this study, we explored BMVC-12C-P can specifically enter the mito-chondria to cause the mitochondrial dysfunction and we also confirmed the mitochondria is the main target of BMVC-12C-P. Therefore, BMVC-12C-P was used as a tool and com-bined with C. albicans mutant library to investigate the biological effects of mitochondrial dysfunction induced by BMVC-12C-P. We had established the optimal screening model to screen and selected the candidates from mutant library of transcription factors and kinases. Because we are interested in the relationship between mitochondria and pathogenic mecha-nisms, candidates are classified according to the pathogenic mechanisms involved. As a re-sult, the pathogenic mechanism of candidates involved in the formation of hyphae was most, so we selected the regulation of hyphae to explore. We confirmed BMVC-12C-P can inhibit the formation of hyphae and biofilm. We also found the ability of hyphae switch was sup-pressed which correlated with the reduced mRNA expressions of genes involved in hyphal formation (EFG1、BRG1、CPH1、CPH2 and TEC1) and not through Hog1MAPK pathway to regulate them. In this way, we hope to further understand the mechanism of BMVC-12C-P on the regulation of hyphae and can be used as an important cornerstone for the development of new antifungal drugs in the future. Moreover, we also found that BMVC-12C-P displayed the strongest antifungal activities to against Candida species and even Fluconazole-resistant clinical isolates of Candida species that indicated BMVC-12C-P can be used as a highly potential antifungal agent.