The discovery is described in a recent joint paper published in Scientific Reports, an online, open access journal from the publishers of Nature.
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 is not derived from any natural sources and is therefore evolutionarily foreign to bacteria.
“The results of this work have several important implications,” said U of R microbiologist John Stavrinides.
“First, because the antibiotic is synthetic, it may be less prone to antibiotic resistance mechanisms already used by drug-resistant bacteria,” he said.
“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.”
Dr. Jane Alcorn, a professor of pharmacy at the U of S, said 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, determine how effective this synthetic antibiotic would be in the human body, and assess the impact, if any, on human cells,” she said.
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 U of R chemist Brian Sterenberg, who then enlisted the help of Alcorn to evaluate the toxicity of the synthetic compounds. Other members of the team included PhD student Arumugam Jayaraman, graduate student Shelby Reid, and undergraduate students Shelby Hubick and Alexander McKeen.
“As far as we know, the types of compounds we synthesized have not been explored as potential antibiotics,” said Sterenberg. “Our future work will be to continue to synthesize new molecules to look for other new antibiotics.”
This work was supported by grants from the Natural Sciences and Engineering Research Council, the Canada Foundation for Innovation and the Saskatchewan Health Research Foundation.
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