SAN FRANCISCO, April 2, 2017 -- Antibiotics save lives every day, but there is a downside to their ubiquity. High doses can kill healthy cells along with infection-causing bacteria, while also spurring the creation of "superbugs" that no longer respond to known antibiotics. Now, researchers may have found a natural way to cut down on antibiotic use without sacrificing health: a maple syrup extract that dramatically increases the potency of these medicines.
The researchers will present their work today at the 253rd National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 14,000 presentations on a wide range of science topics.
"Native populations in Canada have long used maple syrup to fight infections," says Nathalie Tufenkji, Ph.D. "I've always been interested in the science behind these folk medicines."
The idea for the project really gelled when Tufenkji, who had been studying the antimicrobial effects of cranberry extracts, learned of the anti-cancer properties of a phenolic maple syrup extract. "That gave me the idea to check its antimicrobial activity," Tufenkji says. "So, I sent my postdoc to the store to buy some syrup."
Using the same extraction approach as other researchers have in the past, Tufenkji's team at McGill University separated the sugar and water from the syrup's phenolic compounds, which contribute to maple syrup's signature golden hue.
In an initial test, the team exposed several disease-causing bacterial strains to the extract, but they didn't see much of an effect. Rather than give up on maple syrup altogether, Tufenkji decided to check whether the extract could enhance the antimicrobial potency of the commonly used antibiotics ciprofloxacin and carbenicillin. When her team mixed the phenolic extract with either of these medicines, they indeed found a synergistic effect, allowing them to get the same antimicrobial effect with upwards of 90 percent less antibiotic. The approach worked on a variety of bacterial strains, including E. coli, which can cause gastrointestinal problems; Proteus mirabilis, responsible for many urinary tract infections; and Pseudomonas aeruginosa, which can cause infections often acquired by patients in hospitals.
Building on this work, Tufenkji's team next tested the extract in fruit flies and moth larvae. The researchers dosed fly food with pathogenic bacteria and antibiotic, with and without the phenolic extract. Flies with meals doused in maple syrup extract lived for days longer than those denied the syrupy topper. The researchers observed a similar outcome with the moth larvae.
To figure out how the extract makes antibiotics work better, the researchers investigated whether the extract changed the permeability of bacterial cells. The extract increased the permeability of the bacteria, suggesting that it helps antibiotics gain access to the interior of bacterial cells. Another experiment suggested that the extract may work by a second mechanism as well, disabling the bacterial pump that normally removes antibiotics from these cells.
Currently, the researchers are testing the maple syrup extract in mice. While it is likely to be years before it would be available to patients as a prescribed medical protocol, and a pharmaceutical company would likely need to purify the extract further to avoid any potential allergic reactions, Tufenkji says, she's hopeful that it may have an edge over other would-be medications thanks to its source. "There are other products out there that boost antibiotic strength, but this may be the only one that comes from nature," she says.
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A press conference on this topic will be held Monday, April 3, at 9 a.m. Pacific time in the Moscone Center. Reporters may check-in at the press center, South Building, Foyer, or watch live on YouTube http://bit.ly/ACSLive_SanFrancisco. To ask questions online, sign in with a Google account.
Tufenkji acknowledges funding from Canada Research Chairs, the Natural Sciences and Engineering Research Council of Canada and the William and Rhea Seath Award at McGill University.
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Title
Phenolic rich maple syrup extracts synergize with antibiotics
Abstract
The World Health Organization identified antimicrobial resistance as a severe and rapidly growing threat to global health that could undermine decades of progress in combating infectious diseases and preventing healthcare related infections. The true cost of antibiotic resistance will be 300 million premature deaths and up to $100 trillion in global economic losses by 2050. The declining repertoire of useful drugs motivates the need to identify novel approaches to limit the use and maintain effectiveness of antimicrobials/antibiotics. We showed that a phenolic rich extract from maple syrup (PRMSE) can make disease-causing bacteria more susceptible to common antibiotics. PRMSE was obtained by solvent extraction of commercial maple syrup. Our tests showed that PRMSE gave a major boost to the commonly used antibiotics, ciprofloxacin and carbenicillin, in killing Gram-negative clinical strains of Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa. Amongst the phenolic constituents of PRMSE, catechol exhibited strong synergy with the antibiotics. PRMSE also acted synergistically with antibiotics in inhibiting and destroying biofilms, which are common in difficult-to-treat infections, such as catheter-associated urinary tract infections. This strong synergy between PRMSE and selected antibiotics resulted in up to a 97% decrease in the amount of antibiotic needed to halt bacterial growth. Thus, PRMSE can be used as an antibiotic synergizer/potentiator for treatment of different types of bacterial infections. The mechanisms for the observed synergy of PRMSE with antibiotics will be discussed. The proposed synergism-based treatment may expand the spectrum of existing antimicrobials, prevent the emergence of resistant strains, and minimize potential cytotoxicity due to high antibiotic doses.