Grant: Project Grant

Antibiotic resistance is a major global health concern. The mortality and health care costs associated with spread and persistence of antibiotic resistant strains of bacteria, many of which are widely disseminated in hospitals and communities in Canada, the US and world wide, are increasingly dire. At the same time we have few new therapies in the pipeline to treat these increasingly resistant superbugs now and in the future. The protein machinery that create the bacterial cell wall represent one of the greatest drug targets in history, as validated by the amazing success of beta-lactam antibiotics such as penicillins and cephalosporins in near eight decades of treating life threatening infections. Still by far the most common antibiotic class prescribed for reasons of economy, efficacy and side effects, there is still considerable interest in preserving their action by creating cocktails of beta-lactam antibiotic compounds with inhibitors of drug resistance mechanisms inherent to many infectious bacterial strains. Using our state of the art biophysical toolbox we will determine atomic level pictures of central proteins and protein complexes that mediate beta-lactam antibiotic resistance. Coupled with complimentary biochemical and cellular microbiology analysis, these first to field molecular "blueprints" will inform design of new inhibitors and therapies to target infections from notoriously drug resistant, and often hospital acquired superbugs such as Staphlococus aureus, Clostridium difficile, Mycobacterium tuberculosis and Pseudomonas aeruginosa.