Antagonistic interactions between the flavonoids hesperetin and naringenin and β-lactam antibiotics against Staphylococcus aureus

Flavonoids are a group of polyphenolic plant compounds with a range of biological activities. This study shows that the flavonoids hesperetin and naringenin have antibacterial activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus isolates. Minimum inhibitory concentrations for hesperetin were 250 and 500 g/mL, respectively, and for naringenin were 125 and 250 g/mL, respectively. This effect was reversed by the -lactam antibiotics methicillin, penicillin and oxacillin, but not by cefoxitin. For bacteria growing in the presence of these antibiotics, the flavonoids had no effect on the levels of -lactamase enzymes and PBP-2' compared to controls. Electron microscopy showed abnormal morphology in bacteria treated with subinhibitory concentrations of flavonoids. These results are interesting because previous studies have reported synergistic interactions between flavonoids and -lactam antibiotics. It is suggested that an interaction removes both inhibitors from the bacterial growth milieu.