Antimicrobial activity of oenological polyphenols against Gram positive and Gram negative intestinal multidrug-resistant bacteria

Resum

Bacterial antibiotic resistance is a major current health problem. Polyphenols have demonstrated antibacterial activity, and in this work we studied the effect of oenological polyphenols on the growth of intestinal multidrug-resistant strains of human and animal origin. Two Enterococcus faecium strains, resistant to vancomycin and other antibiotics, and four Escherichia coli strains, resistant to ampicillin and other antibiotics, were included in this study. All strains showed multidrug resistant phenotypes and genotypes to at least two antibiotic families. Two Vitis vinifera extracts obtained from red grape skins (GG) and seeds (TS) were studied. Standards of malvidin, epicatechin and myricetin were also included in this study. The antimicrobial activities of the polyphenolic extracts and standards alone and in combination with the corresponding antibiotic of reference were evaluated against the six multidrug-resistant strains. Minimal inhibitory concentration (MIC) and fractional inhibitory concentration index (FIC) were determined. FIC values were interpreted as follows: synergy (FIC≤0.5); partial synergy (0.5<FIC<1); additive effect (FIC=1); indifference (1<FIC<2) and antagonism (FIC≥2).The oenological extracts tested alone inhibited the growth of the six multidrug-resistant strains: GG (MIC=6.25 mg/mL) and TS (MIC≥1 mg/mL), and their effect was bacteriostatic. Combined with the corresponding antibiotic, GG showed a synergistic effect against all the E. coli and E. faecium strains (FICs=0.4-0.6), and it was able to reduce 3-8-fold the antibiotic MICs. Similarly, malvidin inhibited the growth of all the strains (MICs=0.67-1.34 mg/mL), it showed a synergistic effect in combination with the corresponding antibiotic against all the studied strains (FICs=0.6-0.9) and it was able to reduce 2-4-fold the antibiotic MICs. TS, epicatechin and myricetin were also able to inhibit the growth of all the strains (MICs=0.3-2.68 mg/mL) and their effect in combination with the corresponding antibiotic was either additive or indifferent (1£FICs<2).Acknowledgements: ADER2019-I-IDD-00048 of the C.A.R./FEDER; AFIANZA 2022, PR-10-20 and PR-11-19 of the C.A.R.