Investigating light-activated therapeutic compounds as antifungal agents.

真菌是人类、动物和植物的主要病原体。真菌疾病本质上很难治疗，抗真菌药物的种类有限，抗药性的发展是一个严重的问题。因此，真菌病原体对人类健康和食品安全构成威胁，因此需要开发新的治疗策略。LightOx开发了一系列小分子治疗化合物，克服了目前基于光的治疗的局限性。这些化合物具有光激活的细胞毒特性，并可与细胞特异性靶向大分子相连。人们正在研究这些化合物对包括癌细胞、植物和细菌在内的一系列靶标的效用。该项目建立在一项成功的试验性研究的基础上，以确定LightOx化合物的抗真菌活性。我们的初步研究表明，LightOx化合物很容易被真菌细胞摄取，并已确定对模式酵母、酿酒酵母和裂殖酵母以及人类关键病原体白色念珠菌的生长具有光依赖抑制作用的化合物。因此，该项目的目的是(I)确定LightOx化合物的抗真菌活性的光谱和(Ii)利用功能基因组学和细胞生物学来了解它们的作用模式。

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.