A Matter Of Life Or Death - An Integrated Understanding Of MRSA

Year of award: 2023

Grantholders

  • Prof Simon Foster

    University of Sheffield, United Kingdom

  • Prof Rosalind Allen

    University of Jena, Germany

  • Dr Rebecca Corrigan

    University of Sheffield, United Kingdom

  • Prof Ethan Garner

    Harvard University, United States

  • Prof Jeffrey Green

    University of Sheffield, United Kingdom

  • Prof Jamie Hobbs

    University of Sheffield, United Kingdom

Project summary

Antimicrobial resistance (AMR) threatens human healthcare. Our international team will integrate microbial physiology, biochemistry and genetics with biophysics, mathematical modelling and world-leading imaging capabilities, to gain a transformative understanding of the important human pathogen Staphylococcus aureus. We will focus on Methicillin Resistant S. aureus (MRSA) which is responsible for 100,000 deaths annually, building on our foundation of recent discoveries. AMR provides a powerful tool to understand processes critical to life, which we will use to unlock the interwoven pathways linking growth, division and cellular physiology. Our key goals are: to determine the molecular and biophysical basis for high-level resistance in MRSA; to unravel the mechanisms underpinning bacterial cell wall homeostasis during growth and division; and to understand the coordination of cell wall dynamics with cellular physiology, providing a route to novel therapies. Utilising cutting-edge imaging technologies and predictive, quantitative mathematical models, we aim to link genetics, through protein dynamics, to cell wall architecture, mechanical function and growth in the context of the adaptations in whole cell physiology required to accommodate the components necessary for AMR. By spanning disciplines and length scales, we will generate a comprehensive understanding of growth, resistance and new paradigms for developing control regimes.