Phytolectin-cationic lipid complex revive ciprofloxacin efficacy against multi-drug resistant uropathogenic Escherichia coli

The rising threat to antibiotic armamentarium demand innovative methods to use standard antibiotics against multidrug-resistant (MDR) pathogens. Herein, we demonstrated phytolectin-cationic lipid complex have the ability to renew the ciprofloxacin (CIP) activity against MDR uropathogenic Escherichia coli (R4UPEC). The minimum inhibitory concentrations (MIC) obtained for CIP against R4UPEC studied were very high (MIC = 1000 mu M) which may not be suitable for clinical testing. Strikingly, CIP in combination with Butea monosperma seed lectin (BMSL) and cationic lipid, 2-((N-(2-hydroxyethyl)palmitamido)methyl)-1-methylpyridin-1-ium iodide (cN16E) showed 64-fold lower MIC (15.63 mu M). Checkerboard assay revealed that the BMSL-cN16E (BcN16E) complex and CIP work synergistically against R4UPEC. The complex, BcN16E-CIP exerts antimicrobial activity through outer membrane permeabilization, inner membrane disruption, proton motive force dissipation and enhancing the generation of reactive oxygen species. The therapeutic efficacy evaluated in a zebrafish, intramuscular infection model using R4UPEC, the BcN16E-CIP reduce the bacterial load and decrease neutrophil infiltration in muscles and low down the liver cell necrosis. The results demonstrate significantly lower MIC for CIP when complex with BcN16E and showed exceptional in vivo efficacy against infectious MDR bacteria.

Automated summary

This study demonstrates that phytolectin-cationic lipid complex can restore the activity of standard antibiotics against multidrug-resistant pathogens. The BcN16E-CIP complex exhibits antimicrobial activity through multiple mechanisms and shows exceptional in vivo efficacy against infectious MDR bacteria in a zebrafish model.