Reversing β-lactam antibiotic resistance of Staphylococcus aureus with galangin from Alpinia officinarum Hance and synergism with ceftazidime

Abstract

The purpose of this investigation was to extract and identify the bioactive phytochemicals from smaller galanga (Alpinia officinarum Hance). The antibacterial, synergy effects and primary mechanism of action of galangin and ceftazidime against S. aureus DMST 20651 are also investigated by minimum inhibitory concentration (MIC), checkerboard, killing curve determinations, enzyme assay and electronmicroscopy method. The rhizomes chloroform extract of this plant showed that these compounds were galangin, kaempferide and kaempferide-3-O-β-D-glucoside, which had not been previously reported in this species. Synergistic FIC indices were observed in the combination of test flavonoids (galangin, quercetin and baicalein) and all selected β-lactams (methicillin, ampicillin, amoxicillin, cloxacillin, penicillin G and ceftazidime) (FIC index, <0.02-0.11). The combination of ceftazidime at 5 μg/ml and 5 μg/ml of test flavonoids (galangin, quercetin and baicalein) exhibited synergistic effect by reduced the cfu/ml of this strain to 1×10(3) over 6 and throughout 24 h. Galangin showed marked inhibitory activity against penicillinase and β-lactamase. Electronmicroscopy clearly showed that the combination of galangin and ceftazidime caused damage to the ultrastructures of the cells of this strain. It was concluded that galangin, quercetin and baicalein exhibited the potential to reverse bacterial resistance to β-lactam antibiotics against penicillin-resistant S. aureus (PRSA). This may involve three mechanisms of action that galangin inhibit protein synthesis and effect on PBP 2a, interact with penicillinase and cause cytoplasmic membrane damage. These findings lead us to develop a new generation of phytopharmaceuticals that may use galangin, quercetin and baicalein in combination with ceftazidime to treat PRSA that currently almost untreatable microorganism. The anti-PRSA activity and mode of action of galangin is reported for the first time. These in vitro results have to be still confirmed in an animal test or in humans.