Antagonistic interactions between the flavonoids hesperetin and naringenin and beta-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 microg/mL, respectively, and for naringenin were 125 and 250 microg/mL, respectively. This effect was reversed by the beta-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 beta-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 beta-lactam antibiotics. It is suggested that an interaction removes both inhibitors from the bacterial growth milieu.