Impact of Environmental and Cellular Factors on the Bioactivity of a Novel Antifungal, Occidiofungin
Robinson, Chase Alexander
AdvisorGordon, Donna M.
Donaldson, Janet R.
Occidiofungin is a novel glycolipopeptide, synthesized and secreted by Burkholderia contaminans MS14, demonstrating broad-spectrum antifungal activity and potential for successful clinical applications. Its mechanism of action has not yet been determined but is known to exhibit fungicidal activity via the induction of apoptosis in a manner unique from that of currently approved antifungals. As an early investigation into occidiofungin’s mechanism of action, we aimed to identify environmental and cellular factors that significantly alter the susceptibility of the model organism, Saccharomyces cerevisiae. To that end, we have demonstrated that occidiofungin’s bioactivity requires active cellular growth, that new protein synthesis is necessary to adequately respond to occidiofungin exposure, and that alterations in transcriptional regulation in response to glucose and phosphate deprivation have synergistic and antagonist consequences, respectively, on occidiofungin’s effectiveness. Together, this data provides a foundation on which occidiofungin’s mechanism of action can be illuminated.