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. The first part of this talk will be focused on antifungal peptides, their mechanism of action and potential applications for disease control in plants. The second part of the talk will describe the potential of plant defensins as effective and robust treatments for fungal infections in humans. HXP124 is a novel plant defensin that is particularly effective against the dermatophytic fungal species that cause onychomycosis including Trichophyton rubrum. HXP124 is highly selective for fungal cells having no effect on mammalian cells, including red blood cells, at concentrations more than 50 times the MIC. HXP124 is also fungicidal, killing fungal cells within 1 h of exposure. Surprisingly, HXP124 rapidly and efficiently penetrates human nails allowing it to accumulate at the site of infection in the nail bed within 24 h.
Plant defensins contain four disulphide bonds which stabilise the three-dimensional structure. As such, they are stable at extremes of pH (<2) and temperature (>95°C). HXP124 can be produced recombinantly in yeast with very high yields. Its small size and positive charge makes it easy to purify and highly pure protein can be achieved with a simple two-step purification.
Combined, these attributes make HXP124 an excellent candidate for developing a fast, effective topical treatment for onychomycosis.