Our group is interested in antibiotic resistance, focusing on the β-lactam antibiotics and the serine β-lactamases (SBLs) and metallo-β-lactamases (MBLs) that degrade them. We use a multidisciplinary approach, combining chemical, biochemical, biophysical, and microbiological techniques.
Some recent projects have focused on:
Carbapenemases: The clinical use of carbapenems, β-lactam antibiotics of last resort, is critically threatened by bacterial production of β-lactamases with carbapenemase activity. We are investigating the mechanisms by which these enzymes degrade carbapenems, with the aim of developing new antibiotics that resist carbapenemase catalysis.
NMR-Based Mechanistic Studies: We use NMR spectroscopy as a tool to study β-lactamase activity and mechanism. In particular, we are interested in developing 19F NMR approaches for studying reversible interactions, such as inhibitor binding and lysine carbamylation.
L,D-Transpeptidases: The L,D-transpeptidases, promising antibiotic targets in Mycobacterium tuberculosis, are potently inhibited by some β-lactam antibiotics. We are studying the mechanisms by which these enzymes interact with β-lactams, and developing new strategies for investigating L,D-transpeptidase activity and inhibition.
β-Lactam Biosynthesis: The biosynthetic pathways for β-lactam natural products have evolved alongside the enzymes that confer resistance to them. We investigate how these β-lactam antibiotics are assembled and whether they can overcome current antibiotic resistance mechanisms.