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

破译与人类真菌病原体光滑念珠菌耐药性出现相关的基因网络

• 批准号: 2720598
• 金额: --
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2720598
• 关键词: Decphering; network; genes; involved; emergence

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.

威胁生命的感染日益成为现实。几乎所有医院都存在耐多药细菌，如耐甲氧西林金黄色葡萄球菌，而社区获得性结核病往往难以治疗。念珠菌属的真菌不太为人所知，但在英国造成的死亡人数是MRSA的四到五倍。这些通常与粘膜感染（如鹅口疮）有关，但每年在世界范围内造成40万例危及生命的感染，特别是在免疫抑制的患者群体中。主要病原体之一是光秃念珠菌。这种真菌以单细胞单倍体酵母的形式生长，对宿主的先天防御具有高度的抗性，并且对许多临床使用的抗真菌药物具有耐药性，包括前线的唑类药物和棘白菌素。即使在最好的医疗护理下，这种酵母菌感染也会导致50%的死亡率，而光毛梭菌感染的发病率正在稳步攀升。这就要求开发新的抗真菌疗法，可以针对耐药真菌感染，如C. glabrata。为了解决这个问题，该项目利用对常见抗真菌抗性机制的遗传见解来确定可以靶向预防抗性的致命弱点。这种方法可以为开发耐药感染的治疗方法提供一个强有力的工具。