Investigating light-activated therapeutic compounds as antifungal agents.

Fungi are key pathogens of humans, animals and plants. Fungal diseases are intrinsically difficult to treat, there are limited classes of antifungals and the development of resistance is a serious problem. As such, fungal pathogens are threats to human health and food security and there is a need to develop new therapeutic strategies. LightOx has developed a portfolio of small molecule therapeutic compounds which overcome the limitations of current light-based treatments. The compounds have light-activated cytotoxic properties and can be linked to cell-specific targeting macromolecules. The utility of these compounds is being investigated for a range of targets including cancer cells, plants and bacteria. This project builds on a successful pilot study, to determine the antifungal activity of LightOx compounds. Our pilot study revealed that LightOx compounds are readily taken up by fungal cells and has identified compounds with light-dependent inhibitory effects on the growth of the model yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and the key human pathogen, Candida albicans. Therefore, the aims of this project are (i) to determine the spectrum of antifungal activity of LightOx compounds and (ii) to use functional genomics and cell biology to inform on their mode of action.