Fruit flavonoids as modulators of norfloxacin resistance in Staphylococcus aureus that overexpresses norA

Abstract This study investigated whether different fruit flavonoids are capable of modulating norfloxacin (Nor) resistance in Staphylococcus aureus SA-1119B, an S. aureus strain that overexpresses norA . The minimum inhibitory concentration (MIC) of flavonoids and norfloxacin (Nor) were determined using broth microdilution tests. To assess the antibiotic resistance modulatory effect, the MIC of Nor was measured in growth media with or without flavonoids at a sub-MIC level. The lowest MIC (256 μg/mL) against S. aureus SA-1199B was observed for myricetin; all other tested flavonoids produced MICs >256 μg/mL. When tested at sub-MIC levels in combination with Nor, hesperetin reduced the MIC of Nor from 128 μg/mL to 8 μg/mL (16-fold), whereas phloretin, diosmetin, and myricitrin reduced the MIC of Nor from 128 μg/mL to 32 μg/mL (4-fold), and quercitrin reduced the MIC of Nor from 128 μg/mL to 64 μg/mL (2-fold). No modulatory effects were observed for flavonoids with 7- O -glycoside residue or for non-glycosylated forms of 3- O -glycoside flavonoids. These results suggest that fruit flavonoids in aglycone forms or 3- O -glycoside flavonoids are capable of modulating Nor-resistance in S. aureus that overexpresses NorA.