Project Leaders: 
Neil Reiner, Robert Young 

Lead Institutions: 
University of British Columbia, Simon Fraser University
 
Research Funding Program: 
SOF 3 

"Developing new therapeutics to fight MRSA infections"

Multidrug-resistant (MDR) strains of bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) are becoming more prominent in BC’s hospitals and community settings. In the US, MRSA was responsible for an estimated 94,000 life-threatening infections and 19,000 deaths in 2005, which is more deaths resulting from HIV infections that year*. Paradoxically, while antibiotic resistance is on the rise, antimicrobial discovery research is on the decline, and only a few new drugs to fight these bacteria have emerged in the last few years. There is an important need for the discovery and development of new classes of antibiotics to combat these bacterial pathogens.

The UBC Proteomics for Emerging Pathogen Response (PREPARE) team, led by Dr. Neil Reiner, consists of world-renowned infectious disease scientists. They have successfully applied state-of-the art proteomics, computer-aided drug design and a new genomic technologies to identify the bacterial protein, pyruvate kinase (PK), as an ideal target for novel therapeutics. Using these genomics technologies, the PREPARE team has also discovered a novel chemical entity that inactivates the PK target and leads to the destruction of the MRSA bacteria. The goal of this project is to optimize the potency of this novel chemical entity in preparation for human clinical trials.

In collaboration with Dr. Robert Young at SFU, the PREPARE team will apply medicinal chemistry, pharmacokinetics and efficacy studies to further develop this novel chemical entity as a drug to be used to fight MSRA infection. Using computer-aided visualizations, the PREPARE team will optimize the structure of the compound to enhance its potency against bacteria, and to improve metabolic stability and reduce toxicity in humans. The optimized compound will then be tested to determine how well it works in MSRA infection models. If the tests are a success, the next step in the development process will be to start Phase 1 human clinical trials.

The ultimate goal of this project will be to develop novel and improved therapeutics for MRSA and enhance BC’s visibility in infectious disease research. This project will also foster strong linkages and partnerships between local scientists at UBC and Simon Fraser University.  


* Cited from the Journal of the American Medical Association, October 2007