Innate immunity proteins form the first line of defence against potential pathogens in animals and plants. Most research has focused on those with antibacterial properties, but there is an increasing need for effective antifungal agents for use in agriculture and in the clinic. Plant defensins are a large group of innate immunity proteins that protect plants from the devasting effects of fungal pathogens. They are characterised by a conserved three-dimensional structure, stabilised by disulphide bonds. The loops that decorate this conserved structure vary tremendously in sequence, with only the eight cysteines and a glycine strictly conserved and essential for the defensin fold. This extreme sequence divergence leads to diversity of biological activities, and even diversity in the mechanism of action for their antifungal activity. A subset of plant defensins are of particular interest, as they rapidly kill a range of agricultural and human pathogens.
This talk will describe the extreme diversity present in defensins and how this provides both challenges and opportunities for research. I will highlight new insights into the evolution of plant defensins and their ancient relationships with defensins across fungi, insects and mammals. Some of the best-characterised mechanisms for a range of activities will be described.
Basic research on the antifungal properties of defensins led to the establishment of the biotechnology company Hexima and a partnership with Pioneer-DuPont to develop their potential for crop protection. The knowledge gained in this research has led to a rapid transition to the application of defensins for treatment of fungal diseases in humans. Progress towards clinical trials for treatment of onychomycosis (toe nail infections) in 2017 will be described.