Terpenoids with antifungal activity trigger mitochondrial dysfunction in Saccharomyces cerevisiae

Abstract

A number of pathogenic fungi like Candida, cannot survive upon damage to mitochondrial DNA (mtDNA) while the budding yeast can tolerate the damage therefore we chose Saccharomyces cerevisiae as a model system for this study. Since a number of potent antifungals have originated from various natural sources, we decided to use a triterpenoid and tetraterpenoid in this study as an antifungal agent. Our data clearly indicates that terpenoids play a role in diminishing the mitochondrial content which results in altered level of reactive oxygen species (ROS) and ATP generation. Here, we report that triterpenoid and tetraterpenoid display MIC at 100 and 120 μg /mL respectively against S. cerevisiae. At MIC dose triterpenoid (Lupeol) treated cells showed relatively higher mitochondrial dysfunction as compared to tetraterpenoid, resulting high level of ROS generation in triterpenoid in comparison to tetraterpenoid treated cells. Whereas the ATP level decreases in triterpenoid treated cells while it remains same in tetraterpenoid treated cells. Hence triterpenoid showed more potent antifungal activity as compared to the tetraterpenoid at their MIC by targeting mitochondrial integrity. The outcome of the study is to decipher the mode of action of terpenoids which will be useful in designing of improved antifungal therapies and also accelerate the development of translational applications.