Saskatchewan researchers hone in on antibiotic for Staph infections

By Kathryn Warden and Costa Maragos Posted: February 17, 2017 11:00 a.m.

The University of Regina/University of Saskatchewan team includes John Stavrinides, assistant professor in the department of biology and Dr. Brian Sterenberg, associate professor in chemistry and biochemistry in the U of R’s faculty of science.
The University of Regina/University of Saskatchewan team includes John Stavrinides, assistant professor in the department of biology and Dr. Brian Sterenberg, associate professor in chemistry and biochemistry in the U of R’s faculty of science. Photos courtesy of U of R Photography and External relations

A joint research project could lead to a new way to treat certain infections.

An interdisciplinary team of researchers from the University of Regina and the University of Saskatchewan has created a potent new synthetic antibiotic in the lab that is effective against several drug-resistant pathogens such as the bacteria responsible for Staph infections and other difficult-to-treat human infections.

The discovery is described in a recent joint paper published in Scientific Reports, an online, open access journal from the publishers of Nature

Dr Jane Alcorn
Dr. Jane Alcorn is professor of pharmacy at the University of Saskatchewan. Photo - U of S

The researchers state that the group of synthetic compounds they are working on could have “enormous capacity to provide new chemical architectures for the development of next-generation antibiotics” and to “regain some ground on the antibiotic resistance problem.”

That’s because the new compound, phosphopyricin, is a synthetic antibiotic that does not occur naturally and is therefore evolutionarily foreign to bacteria.

“The results of this work have several important implications,” says U of R microbiologist and assistant professor in the department of biology, Dr. John Stavrinides.   

“First, because the antibiotic is synthetic, it may be less prone to antibiotic resistance mechanisms already used by drug-resistant bacteria. Second, widespread antibiotic use results in antibiotic residuals accumulating in the general environment, contributing to the evolution of multi-drug resistance. But this antibiotic breaks down when exposed to light, so it is less likely to accumulate in the environment compared with other antibiotics. This may also help slow the evolution of resistance to our antibiotic.”

Jane Alcorn, U of S professor of pharmacy, says the antibiotic does not appear to be toxic to mice when given orally.  

“The next step will be to identify the specific mechanism of action, and also determine how effective this synthetic antibiotic would be in the human body,” she says.

steph
The compound developed by the research team is found to be effective against two types of bacteria (shown here) responsible for Staph infections. Photo courtesy of Ashley Williams


The team found the antibiotic compound to be effective against methicillin-resistant Staphylococcus aureus (MRSA) which causes infections that can be life-threatening if left untreated, and vancomycin-resistant Enterococcus (VRE) bacteria, which live in the human intestine and urinary tract, are often found in the environment, and are resistant to the antibiotic vancomycin.

These are among bacteria that are acronymously dubbed “ESKAPE” pathogens because they pose a serious threat to human health through repeated emergence, but have the ability to “eskape” antibiotic treatment.

The interdisciplinary work was initiated several years ago by Stavrinides and Dr. Brian Sterenberg, associate professor in the department of chemistry and biochemistry in the U of R’s faculty of science.

Stravrinides then enlisted the help of Alcorn to evaluate the toxicity of the synthetic compounds. But the genesis of the project was a casual conversation between Sterenberg and Stavrinides.

“One potential impact of this work is that it may encourage others to look for antibiotics in unconventional areas,” says Sterenberg. “Our discovery was made possible by our varied research backgrounds and our ablilty to work together to make something happen.”

Other members of the team include:

-U of R biology students Shelby Hubick and Alexander McKeen.

-U of S graduate student Shelby Reid in the department in the College of Pharmacy and Nutrition.

-Dr. Arumugam Jayaraman was a PhD student from the department of chemistry and biochemistry at the U of R at the time of the research. He’s now a post-doctoral fellow at Université Laval in Quebec.

The research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundation for Innovation and the Saskatchewan Health Research Foundation.

Two of the students were supported thanks to contributions from the NSERC undergraduate student research award and a Saskatchewan Innovation and Opportunity Scholarship.