Grant: Operating Grant - PA: Regional Partnership Program - Saskatchewan

Infectious diseases continue to be a major world health problem. Multi-drug resistant bacteria, including the bacteria that cause tuberculosis (Mycobacterium tuberculosis), severe lung infections (Klebsiella pneumonia) and food and water poisoning (Escherichia coli), are making the current drugs used for fighting these and other infections useless, and therefore development of new antibiotics is critical. The best targets for designing new drugs are metabolic pathways that only exist in the pathogen. An especially promising target is the pathogens cell wall, which is very different from human cell walls. These cell-wall structures are critical for pathogen survival. UDP-galactopyranose mutase (UGM) is a protein involved in the pathogen's cell wall formation and isn't found in humans. This proposal seeks to use the structure of UGM with complementary compounds (ligands) bound to it, together computational modeling studies of the protein-ligand complexes, to develop an accurate model of how these compounds bind to the protein. We will use this information to identify new compounds that bind to and prevent UGM from functioning. Promising compounds developed in this program will aid us in creating novel drugs to combat clinical infections.