Modulation of the Drug Resistance by Platonia insignis Mart. Extract, Ethyl Acetate Fraction and Morelloflavone/Volkensiflavone (Biflavonoids) in Staphylococcus aureus Strains Overexpressing Efflux Pump Genes

Abstract

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 evaluated. 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.

Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus

“…Despite not showing activity against this specific strain, addition of these compounds to the growth medium at 256 μ g/mL (MIC 1/4) potentiated the antibacterial effect of norfloxacin against the SA-1199B strain, reducing the MIC values for norfloxacin by at least two-fold ( Table 1 ). Modulating effect on the resistance to norfloxacin could be explained by inhibition of NorA efflux pump overproduced by SA-1199B, as already reported for several compound classes, such as alkamides [ 18 ], chalcones [ 44 – 46 ], flavonoids [ 47 – 50 ], and lignans [ 51 ]. In fact, visnagin, and khellin showed a modulating effect like that exhibited by the known NorA inhibitor chlorpromazine.…”

Chemical composition and potentiating action of Norfloxacin mediated by the essential oil of Piper caldense C.D.C. against Staphylococcus aureus strains overexpressing efflux pump genes

“…To verify if the modulating effect is related with efflux pump inhibition, assays were performed replacing Norfloxacin by EtBr. As the only known mechanism of bacterial resistance to EtBr is mediated by efflux pumps (Markham et al 1999 ), this DNA-intercalating dye have been used to evaluate the potential efflux pump inhibitory activity of natural products (Silva et al 2021a ), isolated phytochemicals (Silva et al 2021b ) and synthetic compounds (Faillace et al 2021 ; Costa et al 2016 ). Results showed that EOPC was also able to modulate the resistance to EtBr in both SA1199B (Fig.…”

Biflavones from Platonia insignis Mart. Flowers Promote In Vitro Antileishmanial and Immunomodulatory Effects against Internalized Amastigote Forms of Leishmania amazonensis

“…The samples used to perform the biological assays, hydroalcoholic extract (EHPi), ethyl acetate fraction (FAcOEt) and biflavonoids mixture (MB) were obtained by developing the work of Silva et al [ 16 ], performed in the Laboratory of Organic Geochemistry of the Federal University of Piauí (LAGO/UFPI). The flowers of Platonia insignis Mart.…”

“…In our group, Silva et al [ 16 ] isolated and identified a mixture of two biflavonoids (moreloflavone and volkensiflavone) and a polyisoprenylated benzophenone garcinielliptona FC (GFC) from the hydroalcoholic extract of P. insignis flowers. These compounds have proven to be responsible for important pharmacological activities attributed to the species.…”