Polyphenolic Extract from Maple Syrup Potentiates Antibiotic Susceptibility and Reduces Biofilm Formation of Pathogenic Bacteria

Abstract

Phenolic compounds are believed to be promising candidates as complementary therapeutics. Maple syrup, prepared by concentrating the sap from the North American maple tree, is a rich source of natural and process-derived phenolic compounds. In this work, we report the antimicrobial activity of a phenolic-rich maple syrup extract (PRMSE). PRMSE exhibited antimicrobial activity as well as strong synergistic interaction with selected antibiotics against Gram-negative clinical strains of Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa. Among the phenolic constituents of PRMSE, catechol exhibited strong synergy with antibiotics as well as with other phenolic components of PRMSE against bacterial growth. At sublethal concentrations, PRMSE and catechol efficiently reduced biofilm formation and increased the susceptibility of bacterial biofilms to antibiotics. In an effort to elucidate the mechanism for the observed synergy with antibiotics, PRMSE was found to increase outer membrane permeability of all bacterial strains and effectively inhibit efflux pump activity. Furthermore, transcriptome analysis revealed that PRMSE significantly repressed multiple-drug resistance genes as well as genes associated with motility, adhesion, biofilm formation, and virulence. Overall, this study provides a proof of concept and starting point for investigating the molecular mechanism of the reported increase in bacterial antibiotic susceptibility in the presence of PRMSE. Gram-negative and Gram-positive bacteria colonize surfaces in health care settings, on indwelling medical devices, and even on live tissue, leading to infections that often are treated with antibiotic therapy. However, two major factors complicate the effectiveness of antibiotic treatments, namely, (i) the rising number of antibiotic-resistant bacteria and (ii) the formation of biofilms. These complications lead to increased patient morbidity, increased costs of treatment, and higher rates of hospitalization (1, 2). Antibiotic resistance is the inevitable evolutionary survival mechanism of bacteria, and it is aggravated by the overuse of antibiotics in the medical and farming industries. Bacterial biofilms are structured, surface-associated microbial communities, protected by a self-produced matrix of extracellular polymeric substances, and are the most common mode of bacterial growth. Formation of biofilms complicates the treatment of infections, because bacteria in biofilm mode generally are very persistent, requiring considerably higher doses of antibiotics for treatment than planktonic bacteria (3). High antibiotic doses disturb the body's microbiome, putting the patient's health at risk, as well as increasing the potential for development of antibiotic-resistant strains (4). The reduced effectiveness of current therapies and a declining repertoire of clinically useful drugs motivate research for the identification of novel molecules endowed with antimicrobial and/or antibiofilm properties.Many plants synthesize aromatic substances, most of which ar...

Escherichia coli biofilm: development and therapeutic strategies

“…The transcriptome analysis revealed that PMRSE effectively repressed multiple drug resistance genes and genes associated with motility, adhesion and biofilm formation (Maisuria et al . ).…”

Proanthocyanidin Interferes with Intrinsic Antibiotic Resistance Mechanisms of Gram‐Negative Bacteria

“…[67] An overnight-grown culture of each strain was diluted 1:100 in MHB-II broth to a final volume of 10 mL and was grown to an OD 600 of 0.8-1.0 (at 37 °C, 150 rpm). [67] An overnight-grown culture of each strain was diluted 1:100 in MHB-II broth to a final volume of 10 mL and was grown to an OD 600 of 0.8-1.0 (at 37 °C, 150 rpm).…”

Tackling Antibiotic Resistance with Compounds of Natural Origin: A Comprehensive Review

“…Cumin demonstrated antimicrobial activity on its own and also resistance modulation properties against MRSA by inhibiting LmrS efflux pump [ 155 ]. Plant molecules inhibiting the ethidium bromide efflux pump (EtBr) have also been found: 1′-S-1′-acetoxyeugenol acetate inhibits it in Mycobacterium smegmatis [ 165 ], catechol and catharanthine inhibits it in P. aeruginosa [ 166 , 167 ] and galotannins inhibit it in MDR uropathogenic E. coli [ 168 ]. The Yojl efflux pump of MDR E. coli has been shown to be inhibited by molecules such as 4-hydroxy—tetralone, ursolic acid and its derivatives [ 169 ] and lysergol [ 170 ].…”