Antibiotic Resistance in Superbugs: Regulation of the Blar beta-lactam sensor of MRSA and the MexAB-OprM multidrug-efflux effector PA3719 from Pseudomonas aeruginosa

Every year, Canada spends hundreds of millions of dollars in the fight against antibiotic-resistant “superbugs”, bacteria that have evolved to outmaneuver the drugs that are designed to kill them. The elaborate resistance machinery that bacteria have developed can be energy consuming for the organism to construct and maintain, so bacteria will activate this defense system only in the presence of antibiotics. This effect is seen within superbugs that are resistant to beta-lactam antibiotics such as penicillin. Mark Wilke is working to understand the regulatory machinery bacteria use to switch on beta-lactam resistance, specifically within the notorious superbugs MRSA (methicillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa. He is using a technique called X-ray crystallography, which generates atomic resolution “snapshots” of proteins and other molecules in action. His findings could lead to new strategies for combating superbug infections.