Superbug Antibiotic Defence Uncovered

Dr. Berghuis’ research team in McGill’s Departments of Biochemistry and Microbiology & Immunology observed a mechanism by which Staphylococcus aureus (SA) can resist the antibiotic Synercid, by attacking one of the drug’s ingredients with an enzyme, Virginiamycin B lyase (Vgb). 

“Specifically, we determined the three-dimensional structure of the enzyme and visualized how it interacts with Synercid,” said Dr. Berghuis, Canada Research Chair in Structural Biology. “This reveals for the first time how Staph aureus can detoxify quinupristin, one of the component drugs of Synercid. More important, though, is that it also suggests how we can optimize Synercid in such a way that it will remain active in resistant bacteria that possess Vgb.”

The researchers chose to use Synercid in their study because the drug, which received accelerated approval from the Food and Drug Administration in 1999, was specifically designed to treat infections caused by superbugs.

Dr. Berghuis, whose lab conducted the study in collaboration with colleagues at McMaster University, said the team will now focus on developing a compound to replace quinupristin in Synercid. They will also continue examining other drugs to see if a similar modification can help counteract drug resistance – at least in the short term.

“There is a small selection of drugs that still work against superbugs, and Synercid is one of the newest, but bacteria are very resourceful,” said Dr. Berghuis. “What we observed is only one trick they use to develop resistance, but if we keep on winning these battles, I think we can stay ahead.”

The findings appear in the early online edition of the journal Proceedings of the National Academy of Sciences (PNAS). Funding for the research was provided by the Canadian Institutes of Health Research (CIHR) and the federal Canada Research Chairs program.