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

总的来说，真菌疾病对动物、植物和生态系统的威胁比其他类型的传染性微生物更大。人类真菌感染导致数百万人死亡，最常发生在患有严重潜在健康问题（如癌症）或慢性肺部疾病（如囊性纤维化）的患者身上。真菌感染每年摧毁的农作物足以养活数百万人。然而，可用于农业或临床的抗真菌药物数量非常有限，某些类别的抗真菌药物，例如唑类药物。因此用于治疗人类和植物真菌感染。2018年，氮基杀菌剂占用于处理作物的抗真菌剂的34%。令人担忧的是，对所有可用抗真菌药物的耐药性正在增加，在某些情况下，农业环境中发生的唑类耐药性在约40%的病例中跨越到临床。这个项目建立在之前几十年的遗传和感染研究的基础上，其中包括一个博士项目，其中一组新的化学物质被证明具有抗真菌活性。这些化学物质攻击人类、植物和动物真菌病原体感染和入侵所需的真菌信号机制，我们现在将努力了解它们是如何起作用的。我们还将努力使它们更有效，并与工业界合作开发它们用于农业或临床。

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.