Targeting Staphylococcus aureus copper resistance as a novel antimicrobial strategy in skin infection models

金黄色葡萄球菌使用宿主抗菌铜作为调控信号来改变基因表达以促进定植。拟议的项目将针对这种反应，以确定治疗严重金黄色葡萄球菌皮肤感染的新抗菌剂。耐甲氧西林金黄色葡萄球菌是造成严重的软皮肤组织感染的原因，造成重大的经济和临床负担。这个跨学科项目的目的是利用我们在金黄色葡萄球菌铜耐药性、新型皮肤感染模型和创新成像和质谱分析方面的专业知识，来验证我们关于铜耐药性在金黄色葡萄球菌皮肤感染中起重要作用的假设，并确定新的抗菌剂。目标是：1。表征金属和细菌的分布，以及皮肤感染模型中的吞噬细胞反应。在皮肤感染模型中确定CuR是否会改变慢性感染的进展。绘制皮肤感染模型中的代谢物图谱，以确定宿主和病原体的代谢状态。4. 通过筛选80k化合物文库鉴定新的金黄色葡萄球菌抗菌药物。该学生将受益于三所大学的专业知识：微生物学培训，高度创新的皮肤感染模型，以及成像方法，包括超分辨率荧光和扫描电子显微镜，质谱和高通量表型，以识别新型抗菌剂。

Staphylococcus aureus uses host antimicrobial copper as a regulatory signal to alter gene expression to promote colonisation. The proposed project will target this response to identify new antimicrobials to treat serious S. aureus skin infection. MRSA are a cause of severe soft skin tissue infections that pose a major economic and clinical burden. The aim of this interdisciplinary project is to build on our expertise of S. aureus copper resistance, novel skin infection models and innovative imaging and mass spectrometry analysis to test our hypothesis that copper resistance plays an important role in S. aureus skin infections and identify novel antimicrobials. The objectives are to:1. Characterise the distribution of metal and bacteria, and phagocyte responses in skin infection models.2. Determine whether CuR alters progression to chronic infections in skin infection models.3. Map metabolites in skin infection models to identify the metabolic status of the host and pathogen. 4. Identify novel S. aureus antimicrobials by screening the 80k compound library. The student will benefit from expertise spanning three universities: training in microbiology, highly innovative skin infection models, and imaging approaches including super resolution fluorescent and scanning electron microscopy, mass spectrometry and high throughput phenotyping to identify novel antimicrobials.