Dr. Brian Coombes is an Associate Professor and Associate Chair in the Department of Biochemistry & Biomedical Sciences at McMaster University. He is also the Assistant Dean of the Biochemistry Graduate Program in the Faculty of Health Sciences, and currently holds the Canada Research Chair in Infectious Disease Pathogenesis.
How is your lab contributing to the global effort to combat antibiotic resistance?
We are addressing this issue in a couple of areas. First, through collaborations with Dr. Gerry Wright’s Lab and Dr. Eric Brown’s Lab, we are trying to advance the discovery of novel drug candidates into preclinical development. This involves taking lead molecules from the chemistry and screening labs and asking whether they have any proof of concept, or efficacy, in animal models of infection.
For example, the Wright and Brown labs discovered that Loperamide, commonly known as Imodium, in combination with Tetracyclines, a class of antibiotics used to treat a number of bacterial infections, is a potent antimicrobial agent against certain Gram-negative bacteria. However, since Loperamide has almost no systemic penetration – it is limited to the gut – my lab was tasked with developing a unique model to test the efficacy of this drug-antibiotic combination. In this case, we implemented a mouse model of acute gastroenteritis following Salmonella infection.
My lab is also interested in the so-called anti-virulence paradigms of drug discovery. Many bacteria that cause infection have the ability to shut down the host’s innate immune system. We are looking at new and creative ways to “disarm” the anti-immunity arsenals of these pathogens. This involves creating an environment that does not actually kill the bacteria but renders them defenseless, giving the immune system the upper hand in eradicating the infection.
Over the last 10 years, my lab has made a lot of progress in understanding these anti-immunity arsenals of bacteria. And with support from Dr. Wright’s Ontario Research Fund (ORF) Grant, we are in a great position to build on this body of knowledge.