Decphering the network of genes involved in the emergence of drug resistance in the human fungal pathogen Candida glabrata

威胁生命的感染越来越成为现实。几乎所有医院都存在多重耐药细菌，如MRSA，社区获得性结核病通常难以治疗。不太为人所知，但在英国造成的死亡人数是MRSA的四到五倍，是念珠菌属的真菌。这些通常与粘膜感染如“鹅口疮”相关，但每年在全球造成> 400，000例危及生命的感染，特别是在免疫抑制患者群体中。主要病原体之一是光滑念珠菌。这种真菌作为单细胞单倍体酵母生长，并且对宿主先天防御具有高度抗性，并且可以获得对许多临床使用的抗真菌药物的抗性，包括前线唑类和棘白菌素类。即使有最好的医疗护理，这种酵母菌的感染也会导致约50%的死亡率和C。光滑的感染在稳步上升。这就要求开发新的抗真菌治疗方法，以治疗耐药真菌感染，如C。光滑的为了解决这个问题，该项目利用对常见抗真菌耐药机制的遗传见解来确定可以有针对性地预防耐药性的阿基里斯之踵。这种方法可以为开发耐药感染的治疗方法提供一个强大的工具。

Life threatening infections are an increasing reality. Multi-drug resistant bacteria such as MRSA are present in nearly all hospitals, and community acquired TB is often recalcitrant to treatment. Less well known, but causing four to five times more deaths in the UK than MRSA, are fungi in the genus Candida. These are commonly associated with mucosal infections such as "thrush", but are responsible for > 400,000 life-threatening infections worldwide every year, especially in the immunosuppressed patient population. One of the principle pathogens is Candida glabrata. This fungus grows as a single celled haploid yeast, and is highly resistant to host innate defences and can acquire resistance to many clinically used antifungal drugs, including the frontline azoles and echinocandins. Even with the best possible medical care, infections with this yeast cause ~50% mortality and the incidence of C. glabrata infections is steadily climbing. This demands that novel antifungal therapies are developed that can target drug resistant fungal infections such as C. glabrata. To address this, this project leverages genetic insights into common antifungal resistance mechanisms to identify an achilles heel that can be targeted to prevent resistance. Such an approach could provide a powerful tool in developing treatments for drug resistant infections.