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Aim:  The smaller galangal is extracted, purified and identified the bioactive compounds. The purpose of this research was to investigate whether these isolated compounds have antibacterial and synergistic activity against amoxicillin‐resistant Escherichia coli (AREC) when used singly and in combination with amoxicillin. The primarily mode of action is also studied. Method and Results:  The galangin, kaempferide and kaempferide‐3‐O‐β‐d‐glucoside were isolated. The minimum inhibitory concentrations(MIC) of amoxicillin and these flavonoids against AREC were between 500 and >1000 μg ml−1. Synergistic activity was observed on combining amoxicillin with these flavonoids. The combinations of amoxicillin and these flavonoids exhibited a synergistic effect, reducing AREC cell numbers. Electron microscopy showed that these combinations damaged the ultrastructure of AREC cells. The results indicated that these combinations altered outer membrane permeability but not affecting cytoplasmic membrane. Enzyme assays showed that these flavonoids had an inhibitory activity against penicillinase. Conclusion:  These results indicated that these flavonoids have the potential to reverse bacterial resistance to amoxicillin in AREC and may operate via three mechanisms: inhibition of peptidoglycan and ribosome synthesis, alteration of outer membrane permeability, and interaction with β‐lactamases. Significance and Impact of the Study:  These findings offer the potential to develop a new generation of phytopharmaceuticals to treat AREC.

BackgroundStaphylococcus epidermidis is one of the most multiple resistances to antibiotics in the recent years. Therefore, practically-prescribed antibiotics in the treatment of these strains are not effective. Plant-derived antibacterial is one of the most interesting sources of new therapeutics. The present study was to investigate antibacterial, synergy and modes of action of quercetin and amoxicillin against amoxicillin-resistant Staphylococcus epidermidis (ARSE).MethodsThe MICs, checkerboard assay, viability curves, cytoplasmic membrane (CM) permeability, enzyme assay, transmission electron microscopy, confocal microscopy and FT-IR microspectroscopy measurement was performed.ResultsThe MICs of amoxicillin, penicillin, quercetin and kaempferol against all ARSE strains were 16, 200, 256-384 and >1024 μg/mL respectively. Synergistic effects were exhibited on amoxicillin plus quercetin and penicillin plus kaempferol against these strains at FIC index 0.50 and <0.38 respectively. The synergistic activity of quercetin plus amoxicillin was confirmed by the viable count. This combination increased CM permeability, caused marked morphological, peptidoglycan and cytoplasmic membrane damage, increased protein amide I and II, but decreased fatty acid in bacterial cells. The quercetin had an inhibitory activity against β-lactamase.ConclusionsSo, these findings are the first report that quercetin has the synergistic effect with amoxicillin against ARSE via four modes of actions, inhibit peptidoglycan synthesis and β-lactamases activity, increase CM permeability and protein amide I and II but decrease fatty acid in bacterial cells. Of course, this flavonol has the dominant potential to develop a brand-new collateral phytochemical agent plus amoxicillin to treat ARSE. Future work should focus on the bioavailability, efficacy and toxicity in animal and human studies, as well as, the synergistic effect on blood and tissue should be evaluated and achieved.

Streptococcus pyogenes causes streptococcal toxic shock syndrome. The recommended therapy has been often failure through the interfering of beta-lactamase-producing bacteria (BLPB). The present study was to investigate antibacterial activity, synergy, and modes of action of luteolin and quercetin using alone and plus ceftazidime against S. pyogenes. The MICs of ceftazidime, luteolin, and quercetin against all S. pyogenes were 0.50, 128, and 128 µg mL−1, respectively. A synergistic effect was exhibited on luteolin and quercetin plus ceftazidime against these strains at fractional inhibitory concentration indices 0.37 and 0.27, respectively, and was confirmed by the viable count. These combinations increased cytoplasmic membrane (CM) permeability, caused irregular cell shape, peptidoglycan, and CM damage, and decreased nucleic acid but increased proteins in bacterial cells. Enzyme assay demonstrated that these flavonoids had an inhibitory activity against β-lactamase. In summary, this study provides evidence that the inhibitory mode of action of luteolin and quercetin may be mediated via three mechanisms: (1) inhibiting of peptidoglycan synthesis, (2) increasing CM permeability, and (3) decreasing nucleic acid but increasing the protein contents of bacterial cells. So, luteolin and quercetin propose the high potential to develop adjunct to ceftazidime for the treatment of coexistence of the BLPB and S. pyogenes infections.