Discovery may help fight antimicrobial drug resistance

Guelph, ON – A new potential target for battling disease-causing bacteria – especially deadly bugs that resist current antibiotics – may result from a study by University of Guelph researchers. The study has shown for the first time the workings of a common bacterial enzyme that may prove vulnerable to drug treatments, said Prof. Anthony Clarke, Molecular and Cellular Biology.

The enzyme might offer a new target for drug companies looking for new ways to fight antimicrobial drug resistance, a growing health threat worldwide, Clarke said.

Published online last month in the Journal of Biological Chemistry, the study was flagged by Global Medical Discovery for drug companies and other researchers. GMD highlights journal articles offering promise for new drug discoveries.

The paper’s lead author is John Pfeffer, who completed a PhD in late 2012 and is working this semester as a post-doc researcher in Clarke’s lab. Their co-author, Joel Weadge, completed his doctorate with Clarke in 2006 and is now a biology professor at Wilfrid Laurier University.

“This new research follows a study where we showed this enzyme might be a new target,” said Clarke. “If so, then the more information we have on how it works, the better placed we are to design or search for inhibitors.”

Bacteria have evolved many variations of defensive enzymes. Knock out one target with an antibiotic, and the bug often deploys a different protein to elude treatment. This particular enzyme – called O-acetylpeptidoglycan esterase, or “Ape” – studied by the Guelph researchers has little redundancy, Pfeffer explained. So drugs might be more effective or doctors might be able to outwit the bugs longer – although he added that bacteria will eventually find a way around potential new treatments.

They studied bacteria that cause gonorrhea. Out of more than one million new gonorrhea infections in the United States in 2009, up to three-quarters involve antibiotic-resistant strains, he said.

Pfeffer said their work might help in treating other organisms, especially drug-resistant strains that pose a greater health threat for people in hospitals and long-term care facilities. “We have to come up with new ways to combat disease,” he added.