Scientists have gained another tool in their battle against antibiotic-resistant superbugs, thanks to the work of researchers from McGill University.
The research conducted by a team led by Dr. Albert Berghuis, chair of the Department of Biochemistry at McGill’s Faculty of Medicine involved literally shining a light on bacterial activity. Their study, titled Structural Basis for Kinase-Mediated Macrolide Antibiotic Resistance, was published in Structure.
The researchers used the intensely bright light at the Canadian Light Source, Canada’s national synchrotron light source facility, located on the grounds of the University of Saskatchewan in Saskatoon, to analyze enzymes called kinases – at the atomic level, according to an article by Lana Haight.
The enzymes in bacteria can to chemically modify antibiotics, said Berghuis. The enzymes take a molecule that has a phosphate group in it and they stick that phosphate group on to something else.
Macrolide antibiotics are the fourth largest class of antibiotics and are prescribed for a variety of infectious diseases, including upper respiratory tract, skin and soft tissue infections. Erythromycin and other macrolide antibiotics are also prescribed as an alternative to penicillin. In 2009, sales of macrolide antibiotics in the U.S. topped $4.8 billion. However, superbugs are able to render them useless.
“In the kinases that we studied, they stick the phosphate group on to the macrolide antibiotic and that little change is just enough to make them no longer an antibiotic,” he said. “When that happens, it becomes a useless compound and the bacteria lives happily ever after which is not good for us.”
He liked the enzyme’s attack against antibiotics to using a coloured marker. With the lid off, the marker is able to colour over what is on the paper – just as a macrolide antibiotic “covers a bacteria and kills it.”
When you place the lid over the marker, the marker is rendered useless – just as the antibiotic is no longer effective when a bacteria’s enzyme attaches to it.
The images and data collected by the team are important information that could be used to out-smart superbugs, said Berghuis.
Scientists now know in “exquisite detail” how macrolides interact with enzymes.
“That exquisite detail is critical if you want to make a version of these macrolides that don’t bind anymore to the enzymes. Without that information, this whole plan goes out the window. That’s what the CLS allowed us to do,” he said. “With this knowledge, we can design a slightly different antibiotic that the enzymes can no longer recognize. We can make a variant of the macrolide that is resistant to the resistance.”