P155: Bacterial pathogen predators: directed searches for evolved bioactive agents

Sunday, August 12, 2012
Columbia Hall, Terrace Level (Washington Hilton)
Morgan A. Wyatt, Xiang Li and Nathan A. Magarvey, Department of Biochemistry and Biomedical Sciences, The Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada
Staphylococcus aureus is a major human pathogen and is becoming increasingly drug resistant. New anti-infectives are needed not just for drug-resistant S. aureus but other multi-drug resistant superbugs. In the past, antibiotics were discovered by random screening of fermentation broths collected from environmental microbes, irrespective of any natural or obvious associations with human pathogens. Despite this, several innovative antibiotics have been identified and due to their broad spectrum of activity have become important chemotherapies. In the bacterial kingdom, like the animal kingdom, there are known to exist predator-prey relationships, whereby certain bacteria exhibit bacteriolytic or cell-dependent killing. In this research, we sought to reveal whether S. aureus (which like many human pathogens is also found in non-human reservoirs) have natural predators that are selective towards it and produce small molecules that assist in killing S. aureus. Through this approach we have identified a series of bacterial groups which exhibit this phenomenon and have used this strategy as a means to discover antibacterial agents not previously known and that are active against drug-resistant S. aureus.  Profiling the secreted small molecules produced by these predatory microbes has lead to chemotypes and antibacterial agents that may be of interest to modern antibiotic discovery. 

This research was funded by CIHR through a Banting and Best Doctoral Fellowship (Wyatt A.M.) and NSERC (Magarvey N. A)