Background: Microbial resistance to antibiotics is a global public health
problem, which requires urgent attention. Platonia insignis is a native species from the
eastern Brazilian Amazon, used in the treatment of burns and wounds.
Objectives: To evaluate the antimicrobial activity of the hydroalcoholic extract of P.
insignis (PIHA), the ethyl acetate fraction (PIAE), and its subfraction containing a
mixture of biflavonoids (BF). Moreover, the effect of these natural products on the
antibiotic activity against S. aureus strains overexpressing efflux pump genes was also
Methods: Minimal inhibitory concentrations were determined against different species of
microorganisms. To evaluate the modulatory effect on the Norfloxacin-resistance, the
MIC of this antibiotic was determined in the absence and presence of the natural products
at subinhibitory concentrations. Inhibition of the EtBr efflux assays were conducted in
the absence or presence of the natural products.
Results: PIHA showed a microbicidal effect against S. aureus and C. albicans, while
PIAE was bacteriosctatic for S. aureus. PIAE and BF at subinhibitory concentrations were
able to reduce the MIC of Norfloxacin acting as modulating agents. BF was able to inhibit
the efflux of EtBr efflux in S. aureus strains overexpressing specific efflux pump genes.
Conclusion:P. inignisis a source of efflux pump inhibitors, including volkensiflavone
and morelloflavone which were able to potentiate the Norfloxacin activity by NorA
inhibition, being also able to inhibit QacA/B, TetK and MsrA. Volkensiflavone and
morelloflavone could be used as adjuvant in the antibiotic therapy of multidrug resistant
S. aureus strains overexpressing efflux pumps.