Grant: Doctoral: Vanier Canada Graduate Scholarships

Expanding antimicrobial resistance is threatening to undo the advances of modern medicine. If we lack effective antibiotics, risks of infection in situations ranging from a simple cut, to a standard surgery, or to patients undergoing chemotherapy will dramatically increase. One of the most common hospital acquired infections in Canada is Methicillin Resistant Staphylococcus aureus (MRSA). In Canada, MRSA infection rates continue to exceed those seen in the early 2000's and it has been estimated to kill more people in the US than HIV/AIDS per annum. Additionally, it is projected that 10 million people could die globally in 2050 due to antimicrobial resistant infections. Bacteria have an essential cell wall containing peptidoglycan, a sugar protein polymer, which is assembled by enzymes called penicillin binding proteins (PBPs). Most antibiotics prescribed today kill bacteria by inhibiting PBPs; however, S. aureus acquired a particular PBP that facilitates the synthesis of peptidoglycan even in the presence of beta-lactam antibiotics, thus forming the infamous "super bug" known as MRSA. MRSA is a major concern as it is resistant to nearly all antibiotics targeting cell wall synthesis. The genes coding for this PBP and the proteins regulating it form the mec pathway. Here I propose to examine the mec pathway in detail by structurally characterizing MecR1, a key regulatory protein responsible for regulation of antibiotic resistance. Additionally, I aim to discover and characterize other proteins involved in this pathway. We are also working with collaborators to screen and develop drugs to interfere with this pathway. Understanding how this pathway works will facilitate the development of novel inhibitors. The experience, equipment, and funding in the Strynadka lab, as well as national and international collaborations, make this the ideal lab for the successful completion of this project which seeks to improve the health of Canadians and public health in general.