Associated organisationsHarvard University · University of Jena · University of SheffieldEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£6.0M
PeriodJan 2024 — Dec 2029
In plain English
AI plain-English summary
Every year, MRSA kills 100,000 people worldwide, and this project aims to understand exactly how the bacterium builds and maintains its defences. Antimicrobial resistance is one of the most pressing threats to modern medicine. While MRSA is infamous for its resistance to methicillin and other beta-lactam antibiotics, the fundamental biology that allows it to survive and grow while carrying resistance machinery remains poorly understood. This project fills that gap by linking the molecular details of resistance proteins to the physical architecture of the bacterial cell wall and the overall physiology of the cell. If successful, the research will produce a predictive, quantitative model of how MRSA coordinates growth, division, and resistance. This could reveal new vulnerabilities in the cell wall assembly process, opening routes to therapies that bypass existing resistance mechanisms. The work is primarily fundamental science—integrating genetics, biophysics, and advanced imaging to answer basic questions about how a bacterium lives while resistant. Historically, such deep mechanistic understanding of bacterial cell wall synthesis has underpinned the development of major antibiotic classes, including the penicillins themselves.
View original technical description
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.
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