Fungal disease is an ever increasing burden in human health. With the appearance of resistance to current treatments, novel approaches are required to treat and prevent fungal disease. Antimicrobial peptides have been the focus of intense research in recent years for their use as antibacterial agents and this focus is now turning to include their use as antifungal agents.
Plants and animals naturally express a vast array of antifungal peptides as part of their innate immune system. One such protein, the plant defensin NaD1, from Nicotiana alata, has potent antifungal activity against agricultural pathogens and is being trialed for protection of transgenic crops. It also has good antifungal activity against Candida albicans and various Cryptococcus species. Its mechanism of action involves binding to the cell wall, permeabilisation of the plasma membrane and entry into the cytoplasm where it potentially interacts with an intracellular target(s). Candida albicans knockout libraries were screened to identify fungal targets involved in the action of this peptide. We found two gene deletions which made C. albicans sensitive to the activity of NaD1. These sensitive mutants both had deletions in the HOG1 pathway, which is responsible for oxidative and osmotic stress response.