Augmentation of antibacterial activity of ciprofloxacin by bisabololoxide A encapsulated in polymeric nanoparticles against uropathogenic Escherichia coli.

BACKGROUND

Multidrug-resistant uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infections, largely due to efflux pump overexpression, porin alterations, and increasing biofilm formation. To address these challenges, we developed bisabololoxide A-loaded PEG400-oleate polymeric nanoparticles (BAPNs) and evaluated their potential to enhance the efficacy of ciprofloxacin against ciprofloxacin-resistant isolates. MATERIALS AND

METHODS

BAPNs were synthesized and characterized by FTIR, TEM, FE-SEM, EDX, TGA, and zeta potential analysis. The synergistic effects of BAPNs and ciprofloxacin were evaluated in drug-resistant isolates. The inhibition of Biofilm formationwas quantified by crystal violet staining and gene expression changes in some genes related to efflux pumps, porins and biofilm formation were analyzed in two representative isolates by qPCR.

RESULTS

BAPNs exhibited a spherical morphology with sizes ranging from 17 to 28 nm (TEM) and 30–43 nm (FE-SEM). Checkerboard analysis showed that the MIC of ciprofloxacin decreased by 2- to 32-fold in ciprofloxacin-resistant isolates and the ATCC 8739 strain when combined with BAPNs. Biofilm inhibition was significantly enhanced with the combined therapy compared to ciprofloxacin alone. qPCR analysis further revealed significant downregulation of the AcrAB-TolC efflux pump genes and the virulence genes fimH and hlyA, along with upregulation of the porin genes (ompC and ompF). Furthermore, molecular docking analysis confirmed the strong binding affinities of bisabololoxide A with virulence-associated proteins of E. coli.

CONCLUSIONS

Our findings suggested that BAPNs may significantly potentiate ciprofloxacin activity by inhibiting efflux pump expression and biofilm formation, and increase of cell membrane permeability to drugs (with enhancing porins), thereby restoring susceptibility in resistant UPEC isolates. These results highlight BAPNs as a promising adjunctive nanocarrier strategy to overcome ciprofloxacin resistance in uropathogenic E. coli. Further validation in larger isolate panels and in vivo studies is warranted.