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

针对金黄色葡萄球菌铜耐药性作为皮肤感染模型中的新型抗菌策略

基本信息

批准号：
2738553
负责人：
金额：
--
依托单位：
University of Leicester
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-2738553
关键词：
Targeting Staphylococcus aureus copper resistance

项目摘要

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.

金黄色葡萄球菌使用宿主抗微生物铜作为调节信号来改变基因表达以促进定殖。拟议的项目将针对这一反应，以确定新的抗菌剂来治疗严重的沙门氏菌。金黄色皮肤感染。MRSA是造成严重的软皮肤组织感染的原因，其造成主要的经济和临床负担。这个跨学科项目的目的是建立在我们的专业知识的S。金黄色葡萄球菌铜耐药性，新的皮肤感染模型和创新的成像和质谱分析，以测试我们的假设，铜耐药性在S.金黄色葡萄球菌皮肤感染，并确定新的抗菌剂。目标是：1.皮肤感染模型中金属和细菌的分布以及吞噬细胞的反应.确定CuR是否改变皮肤感染模型中慢性感染的进展。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.鉴别新型S。通过筛选80k化合物库来筛选金黄色葡萄球菌抗菌剂。学生将受益于跨越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，质谱和高通量表型分析，以识别新型抗菌剂。