Grant: Operating Grant

Pathogenic bacteria, such as P. aeruginosa. E. coli and K. pneumonia, can cause serious infectious diseases such as pneumonia, urinary tract infections, and diarrhea. These bacteria are becoming resistant to many commonly used antibiotics. In addition, the spreading of such pathogenic bacteria that are resistant to multiple antibiotics has become more rapid during the past decade. The resistant bacteria area serious threat to Canadian and global health, and new strategies are needed to combat them. The underlying cause for bacterial resistance is the action of a group of enzymes called beta-lactamases, which destroy beta-lactam antibiotics such as penicillin. Moreover, on-going changes in bacterial beta-lactamase genes in nature are producing more potent enzymes to destroy even our newest antibiotics. This proposal describes research to study the ways that beta-lactamase enzymes change and adapt to antibiotics. We will combine experiments to identify mechanisms of change with detailed studies of enzyme function so that we can develop ways to block their activity. Ultimately, the information obtained in this research program will be used to develop novel, persistent and sustainable antibiotics and inhibitors against pathogenic bacteria.