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

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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.