Date of Graduation
Bachelor of Science
Candida albicans is a normal inhabitant of the skin and mucosal membranes of humans, however, in individuals with depressed immune systems or disrupted cutaneous flora, Candida can overgrow and cause serious infection. Candida infection is the fourth leading cause of nosocomial infection in the United States. These infections are often associated with longer hospital stays and higher mortality. Current drug therapies for this infection are largely ineffective due to the increased drug resistance of Candida species, and for some therapeutics, high levels of drug toxicity to humans. Histatin 5 is a naturally occurring salivary peptide that has strong antifungal properties. Derivatives of this peptide, including KM12 and KM23, have been previously tested in the McNabb lab, and have shown as much as ten times more fungicidal activity than Histatin 5. Our current understanding of the mechanism by which these peptides kill has not been fully characterized. This study uses Saccharomyces cerevisiae as a genetically tractable model to investigate one of the proposed target mechanisms of KM23, namely respiratory metabolism. Respiratory mutants were tested to determine which gene knockouts conferred cell resistance to KM23. If resistance was present for the mutant, the corresponding gene product is part of the killing mechanism of KM23. ATP synthase mutants, atp1Δ, atp2Δ, atp5Δ, and atp7Δ, were the main focus of this study. It was found that atp1Δ, atp5Δ, and atp7Δ conferred resistance of the yeast cells to KM23, while atp2Δ did not show significant resistance. It was subsequently found that atp2Δ was not truly respiratory deficient, therefore, we conclude that ATP synthase function is imperative to the overall killing action of KM23, supporting prior observations that respiratory metabolism is necessary for killing by Histatin 5 and Histatin 5-related peptides.
Mason, Michelle L., "Exploring the mechanisms of action of antifungal peptides using Saccharomyces cerevisiae." (2016). Biological Sciences Undergraduate Honors Theses. 12.