Polyphenolic-rich Maple syrup extract can be used as anti-bacterial agent to mitigate multidrug resistance, biofilm formation and virulence gene expression in different pathogenic bacteria. The synergistic combination of antibiotic and polyphenolic-rich maple syrup extract might have potential to treat urinary tract infections and other chronic infections. This maple syrup extract can be potentially used as natural and safe antimicrobial treatments, combinatorial therapy with existing antibiotics, in preparation of biodegradable polymer scaffold for medical applications such as wound dressings and also as edible or non-edible food coatings directly on fresh produce and other food products (e.g., dairy, meat) or as additives in medical or food packaging materials to prevent adhesion, biofilm formation and proliferation of microorganisms (bacteria, fungi and viruses).
This is the first evidence showing antimicrobial activity of polyphenolic maple syrup extract potentiates antibiotic susceptibility in pathogenic bacteria. Also, this maple syrup extract reduced biofilm formation and the expression of multidrug resistance and virulence associated genes of pathogenic bacteria.
Medical settings (natural anti-infective, anti-microbial, anti-biofilm or anti-virulence agent), Agricultural (natural food preservative and anti-microbial food packaging materials); public safety and national defense (food safety and protection).
No previous evidence exists on the use of phenolic rich maple syrup extract (PRMSE) as anti-bacterial agent, which increases antibiotic susceptibility of pathogenic bacterial strains, and also as anti-biofilm and anti-virulence candidate against uropathogenic bacteria. No previous evidence exists on use of phenolic rich maple syrup extract as edible coating agent to prevent bacterial attachment and proliferation on different surfaces.
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Patent by Seeram et al. (Pub. No.: US 2013/0267474 A1) claims a method to prevent microorganism infection, kill or inhibit bacteria or treat microorganism infection in a subject, which comprises administrating an anti-microorganism amount of a molecule from maple syrup extracts. Another patent by Barbeau et al. (Pub. No.: CA2815392 A1) claims a composition for the prophylaxis of an ailment comprising a therapeutically effective amount of an extract of an Acer tree in association with a pharmaceutically acceptable carrier.
But these embodiments of both patents are not supported by any experimental evidence or proof of concept of anti-microbial or anti-bacterial activity of maple syrup extracts. There is no previous evidence on the mechanism of action by which phenolics of maple syrup mitigate multidrug resistance, virulence associated gene expression and biofilm formation of uropathogenic bacteria.
Phenolic rich extracts of North American maple syrup, obtained from the maple tree (genus, Acer), have been reported to exhibit anti-cancer and anti-diabetic activity; however, their potential anti-bacterial activity has not been examined. Herein, the anti-bacterial efficacy of phenolic-rich maple syrup extract (PRMSE) was investigated for its potential in treating clinical and multiple drug resistant bacterial strains. Experiments involve combinations of phenolic rich maple syrup extract and antibiotic (ciprofloxacin or carbenicillin) at different concentrations analyzed for growth inhibition of each uropathogenic bacterial strains (Escherichia coli CFT073, Proteus mirabilis HI4320, Pseudomonas aeruginosa PAO1 and P. aeruginosa PA14). Another set of experiments demonstrating anti-biofilm activity of PRMSE against uropathogenic bacterial strains were performed. We have observed the anti-bacterial properties of PRMSE which increase antibiotic susceptibility of each uropathogenic bacterial strain at sub-inhibitory concentrations. This extract also significantly reduced biofilm formation in different uropathogenic strains without inhibiting the growth of planktonic cells. Transcriptome analysis revealed that PRMSE significantly repressed multiple drug resistance genes, motility and attachment related genes, and virulence associated genes of uropathogenic clinical strains. Two key components of PRMSE, namely, gallic acid and catechol, were found to increase outer-membrane permeability, and PRMSE was effectively inhibit efflux pump may involved in multi drug resistance in uropathogenic strains. A synergistic combination of antibiotic with catechol exhibited against the growth of tested clinical strains in vitro. Furthermore, combinations of catechol with selected phenolic components of maple syrup were highly synergistic against the growth of clinical strains. The beneficial properties of PRMSE suggest that combination of phenolics and antibiotic may be an effective new anti-bacterial therapy for urinary tract infections and chronic wounds, and impart prospective biological property to maple syrup. The present disclosure relates to the mechanism of action by which an anti-bacterial composition comprising phenolic derivatives of maple syrup mitigates multidrug resistance, virulence and biofilm formation of uropathogenic bacteria. The invention has been developed by Professor Nathalie Tufenkji in collaboration with Dr. Vimal Maisuria. No other partners or collaborators have contributed to this invention.
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The Invention is aimed at three complementary aspects: (1) the direct or indirect application of phenolic rich derivatives of maple syrup as anti-bacterial, anti-biofilm and anti-virulence candidate against infectious bacteria, (2) the incorporation into biomaterials or drug delivery vehicles in a range of applications which require sterile conditions, including but not limited to medical devices, materials used in urinary catheters, angioplasty balloons and implanted devices; materials used in medical grade or food packaging materials to prevent bacterial attachment and proliferation on different surfaces. The preliminary proof of concept is shown in the experimental data summarized in the attached file (Accepted manuscript). We have shown that we can enhance the susceptibility of bacteria for an effective antibiotic treatment. Also, we have shown that mechanism of action by which phenolic derivatives of maple syrup mitigate multidrug resistance, virulence associated gene expressions and biofilm formation of uropathogenic bacteria.
We need to perform further experiments to:
- Analyse the anti-viral properties of phenolic rich maple syrup extracts.
- Optimize the coating treatment of foods with maple syrup derivatives for heightened food safety
- Optimize the incorporation of maple syrup derivatives into materials used in urinary catheters, scaffold materials or food packaging materials and study the potential to prevent attachment and proliferation of bacteria on the surface of the novel catheters or food packaging.
- Assay for effect of maple syrup extract on interaction of pathogenic bacteria with animal or human cells.
Commercial production of maple syrup is principally located in North America, where Canada is the world’s largest exporter of maple products, covers about 85% of the world’s maple syrup production with exports of $249 million in 2012.
The implementation of maple syrup derivatives in the anti-microbial treatments against pathogens or superbug holds potential in strengthening control measures, development of alternative strategies and infection prevention in health care facilities. The maple products may rise as potential source of new anti-microbial agents majorly used in pharmaceutical or agricultural industries. Canada’s agricultural industry relies heavily upon exports providing for 8.1% of the nation’s Gross Domestic Product, a value of over $26.5 billion. Any compromise to the security of these production mechanisms, ranging from livestock to wheat, may prove catastrophic to the Canadian economy by immediately closing borders with trading partners. The implementation of maple syrup derivatives in the processing and packaging of foods holds potential in the prevention of microbial contamination affecting these products. The Canadian agricultural market is easily eclipsed by the American food and fibre market evaluated at over $1.2 trillion; with better structured food safety programs since the release of the Homeland Security Directive 9 (HSPD-9), “Defense of United States Agriculture and Food”, the food safety market in the US has become significantly more developed and active, thereby increasing the need for novel food-safety related products.
The invention involves the use of natural product of biological origin, which is considered non-toxic, edible, and commercially available at large quantities for potential applications in medical and agricultural sectors. As opposed to the usage of antibiotics and hazardous chemicals that may lead to selection of pathogenic resistant bacterial strains, phenolic derivatives of maple syrup provides a value-added potential for foodstuffs, where not only is bacterial growth limited, but antioxidant content of the food is increased as well. In this field, technologies are currently emerging for application of novel anti-microbial agent to combat against multidrug resistant strains in healthcare facilities and also the protection of food supply. Maple syrup is natural, safe and has multiple health benefits such as anti-cancer, anti-diabetic and other beneficial health properties (important factors in energy production, healthy bone formation and immune system, and normal functions of brain and nerve). Maple syrup can be served as new source of anti-bacterial or anti-viral candidates. Thus application of phenolic rich maple syrup extract as anti-bacterial or anti-viral coating agent and incorporation in medical grade or food packaging materials to develop intervention strategies to reduce the health risk of bacterial and viral diseases and also carries additional benefits for the consumer and uses thereof.
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