Targeting bacterial superbugs: novel approaches for optimisation of antibiotic combinations and resistance prevention

While multidrug-resistant 'superbugs' are among the 3 most serious global health threats, no new antibiotic against critical gram-negative bacteria such as P. aeruginosa will be available for many years. Beta-lactams are the largest class of antibiotics and kill P. aeruginosa by binding with specific affinities to 8 different penicillin-binding protein (PBP) receptors. This proposal will identify and evaluate optimal patterns of PBP occupancy by beta-lactams leading to greatest killing and resistance prevention. The mechanistic insights and resistance prevention strategies from this research will yield vital information on optimal combinations of available beta-lactams and enable a new era of targeted design of novel beta-lactams.