Breaking biofilms: novel biofilm modifying enzymes from human skin bacteria to target Staphylococcus aureus infections

Staphylococcus aureus is an important human bacterial pathogen with methicillin resistant strains (MRSA) causing over 100k deaths annually. The bacterium lives on the skin and nose of heathy humans, alongside other commensal Staphylococci, and usually initiates infections through skin damage. Hence, medical procedures that break the skin, such as catheters and other indwelling medical devices are an important nosocomial route of MRSA infections. The formation of a biofilm is essential for colonisation and initiation of infection, with the biofilm matrix usually composed of a polymer of N-acetylglucosamine (PNAG). While studying the biosynthesis of PNAG used by Staphylococci, we discovered a new gene present in the biosynthetic ica operons of various Staphylococci that we hypothesise has PNAG cleaving activity (PNAGase). This we think functions to regulate the length of PNAG polymers released onto the cell surface, directly impacting on biofilm properties and infection. In this project you will join a thriving well-funded group in the Dept. of Biology at the University of York with strong links to glycobiologists, synthetic chemists and clinical researchers. The primary aims are to take a combined microbiological and biochemical approach to characterise the new PNAGase enyzmes, determine the impact of PNAGase on biofilm production by bacteria using advanced microscopy techniques available in the Biology Technology Facility and investigate the impacts of removing this function from pathogenic strains of Staphylococcus aureus. This will include MRSA strains and will use modern genetic technique for gene inactivation. These aims will be enabled through the additional expertise of Dr. Rebecca Corrigan, who specialises in staphylococcal genetics at the University of Sheffield and Prof. Marjan van der Woude, an expert in bacterial biofilm function, in the Hull York Medical School (HYMS). Finally you have the opportunity to test the therapeutic use of the new enzymes in models of S. aureus infection with clinical colleagues at HYMS in the University of Hull.

The project builds on the discovery of novel enzymes in biofilm biosynthetic clusters that have the potential to alter biofilm properties and could have important roles as anti-infectives. There is an urgent need for new therapeutics to combat infectious disease and this project will place you at the centre of these efforts. The project is ideal if you have a back ground and interests in bacterial virulence. Biochemistry and genetics, and are interested in working towards manipulating pathogen processes to address human disease.