Penicillin and successive generations of β-lactam antibiotics have played a vital role in human healthcare for over 80 years; however their effectiveness has decreased markedly due to bacterial resistance. These antibiotics work by targeting penicillin binding proteins (PBPs) – a group of enzymes which are responsible for biosynthesising peptidoglycan, a unique and essential macromolecule present in bacterial cell walls. Bacteria have evolved over time creating new or modified PBPs which are less sensitive to β-lactam antibiotics. The exact mechanism of how this occurs is not understood, nor do we know how PBPs interact with their natural substrates. The project will aim to develop novel chemical probes to image PBPs, specifically PBP2a which is responsible for MRSA, using super resolution microscopy. This will help us understand: (i) the fundamental mechanisms of PBPs, (ii) the structural diversity of peptidoglycan, and ultimately (iii) an understanding of how β-lactam antibiotic resistance occurs. |
The Team
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