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Antibacterial properties of 3′,4′-difluoroquercetin (di-F-Q), a fluorine-substituted stable quercetin derivative, were investigated. Even though di-F-Q itself did not show interesting antibacterial activity, treatment of the  Staphylococcus aureus  strains with di-F-Q resulted in a dose-dependent reduction in biofilm formation with IC 50  values of 1.8 ~ 5.3 mg/L. Also, the antibacterial activity of ceftazidime (CAZ) against carbapenem-resistant  Pseudomonas aeruginosa  (CRPA) showed eightfold decrease upon combination with di-F-Q. Assessment of the antimicrobial activity of CAZ in combination with di-F-Q against 50 clinical isolates of  P. aeruginosa  confirmed 15.7% increase in the percentages of susceptible  P. aeruginosa  isolates upon addition of di-F-Q to CAZ. Further mechanistic studies revealed that di-F-Q affected the antibiotics efflux system in CRPA but not the β-lactamase activity. Thus, di-F-Q was almost equally effective as carbonyl cyanide  m -chlorophenyl hydrazine in inhibiting antibiotic efflux by  P. aeruginosa . In vivo evaluation of the therapeutic efficacy of CAZ-(di-F-Q) combination against  P. aeruginosa  showed 20% of the mice treated with CAZ-(di-F-Q) survived after 7 days in IMP carbapenemase-producing multidrug-resistant  P. aeruginosa  infection group while no mice treated with CAZ alone survived after 2 days. Taken together, di-F-Q demonstrated unique strain-specific antimicrobial properties including anti-biofilm and antibiotic-potentiating activity against  S. aureus  and  P. aeruginosa , respectively.

Strain-specific anti-biofilm and antibiotic-potentiating activity of 3′,4′-difluoroquercetin