Understanding Drug Resistance in Human Fungal Pathogens

耐药病原体的出现是一个日益严重的问题，因为它削弱了我们治疗常见感染的能力。尤其令人担忧的是，当真菌病原体不再对药物产生反应时，抗真菌药物耐药性在全球范围内蔓延。真菌病原体对动物、植物和生态系统的健康构成威胁。事实上，真菌疾病每年导致约150万人死亡。病原真菌也是全球粮食安全的威胁，因为它们可以感染植物和农作物，真菌感染正在导致南海岸生物科学博士培训伙伴(SoCoBio DTP)的灭绝。电子邮件：socobio@soton.ac.uk网站：www.South Coast biosciencesdtp几个动物群体，包括蝙蝠、两栖动物和爬行动物。该项目旨在了解白色念珠菌、两栖动物和爬行动物中抗真菌药物耐药性的机制人类最常见的真菌病原体。白色念珠菌通常生活在人体内，不会造成任何危害。然而，白色念珠菌可以在免疫功能受损的人中引起危及生命的感染，例如正在接受化疗的癌症患者。目前治疗白色念珠菌感染的有效抗真菌药物只有三种，而耐药性的出现阻碍了我们的治疗选择。蛋白质是包括真菌病原体在内的所有生物体中的主要功能分子。蛋白质可以在一种称为翻译后修饰(PTM)的过程中进行化学修饰。PTM调节蛋白的功能、定位和活性。Buscaino实验室最近发现SUMO化是调节白色念珠菌抗真菌耐药性的关键PTM。事实上，白念珠菌通过积累特定的基因组重排来筛选松弛的关键相扑酶，从而对抗真菌药物产生耐药性。这个博士项目结合了我们在真菌遗传学、基因组学(Buscaino)、定量蛋白质组学和生物信息学(Giamas)方面的专业知识，揭示了白色念珠菌蛋白SUMO化如何以及为什么导致耐药性，以及SUMO化机制如何调节白色念珠菌蛋白质组对抗真菌药物的反应。

The emergence of drug-resistant pathogens is an increasing problem as itdiminishes our ability to treat common infections. Especially alarming is theglobal spread of antifungal drug resistance occurring when fungal pathogensno longer respond to drugs.Fungal pathogens are a threat to animal, plant and ecosystem health.Indeed, fungal diseases cause ~ 1.5 million human death annually.Pathogenic fungi are also a worldwide threat to food security, as they caninfect plants and crops, and fungal infections are driving the extinction ofSouth Coast Biosciences Doctoral Training Partnership (SoCoBio DTP)Email: socobio@soton.ac.uk Website: www.southcoastbiosciencesdtpseveral animal groups, including bats, amphibians and reptiles.This project aims to understand the mechanisms of antifungal drugresistance in Candida albicans, the most common human fungal pathogen.C. albicans commonly live in the human body without causing any harm.However, C. albicans can cause life-threatening infections inimmunocompromised individuals such as cancer patients undergoingchemotherapy treatments. There are only three types of effective antifungaldrugs to treat C. albicans infection, and the emergence of drug resistanceseverely hinders our therapeutic options.Proteins are the primary functional molecules in all living organisms,including fungal pathogens. Proteins can be chemically modified in a processknown as Post-Translation Modification (PTM). PTMs modulate thefunction, localisation and activity of proteins.The Buscaino lab has recently identified SUMOylation as a key PTMregulating C. albicans antifungal drug resistance. Indeed, C. albicans strainslacking key SUMO enzymes develop resistance to antifungal drugs byaccumulating specific genomic rearrangements. This PhD project combinesour expertise in fungal genetics, genomics (Buscaino), quantitativeproteomics and bioinformatics (Giamas) to unveil how and why C. albicansprotein SUMOylation leads to drug resistance and how the SUMOylationmachinery regulates the C. albicans proteome in response to antifungaldrugs.