Chemigenetic analysis and efficacy of novel antifungal drugs that target fungal pH signalling

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Collectively, fungal diseases pose a greater threat to animals, plants and ecosystems than other types of infectious micro-organism. Fungal infections of man kill millions and most often occur in patients with severe underlying health conditions such as cancer, or chronic lung disorders such as cystic fibrosis. Fungal infections of plants destroy enough crops annually to feed many millions of people. However, there are a very limited number of antifungal drugs available for use agriculturally or in the clinic and some classes of antifungal drugs, for example the azoles. are therefore used to treat both human and plant fungal infections. In 2018 azole-based fungicides accounted for 34% of the antifungal agents used to treat crops. Worryingly, resistance to all classes of available antifungal drugs is increasing and azole resistance occurring in agricultural settings crosses over into the clinic in around 40% of cases in some settings. This project builds on decades of previous genetic and infection studies, including a PhD project where a new set of chemicals were showed as having antifungal activity. These chemicals attack a fungal signalling mechanism needed for infection and invasion by fungal pathogens in man, plants, animals and we will now work to understand how they work. We will also try to make them more potent, and work with industry to develop them for use in agriculture or in the clinic.