Abstract
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 IC50 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.
Highlights
Antibacterial properties of 3′,4′-difluoroquercetin, a fluorine-substituted stable quercetin derivative, were investigated
Eight gram-negative bacterial strains [P. aeruginosa (CSPA and carbapenem-resistant Pseudomonas aeruginosa (CRPA)), A. baumannii (CSAB and CRAB), K. pneumoniae, and E. coli] were tested for their susceptibility to di-F-Q by using the broth microdilution checkerboard (CB) method (Table 1)
Based on the structural similarity, di-F-Q is presumed to have the similar mode of action as quercetin against gram-positive bacteria
Summary
Antibacterial properties of 3′,4′-difluoroquercetin (di-F-Q), a fluorine-substituted stable quercetin derivative, were investigated. Quercetin has been reported to have a potential as an antibacterial a gent[1], and its anti-biofilm activity against clinical isolates of gram-positive bacteria, albeit low[2], is noteworthy. The antibacterial activity of di-F-Q against various gram-positive and gram-negative bacterial strains was investigated (Table 1).
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