Levofloxacin-Loaded Nanoparticles Decrease Emergence of Fluoroquinolone Resistance in Escherichia coli
Abstract
Antimicrobial resistance is a major global health problem that is developed upon exposure of bacteria to antimicrobial agents, and, thus, reducing or eliminating the ability of the currently available antibacterial drugs to eradicate bacterial infections. The aim of the current study was to encapsulate levofloxacin (third generation fluoroquinolones) into chitosan (CS) nanoparticles, to evaluate the antibacterial potency of the nanosized drug, and to characterize the major genetic mutations associated with the exposure of bacteria to the levofloxacin-loaded nanoparticle versus free levofloxacin. Three consecutive mutants were selected by stepwise exposure of one reference and two clinical Escherichia coli isolates to a series of progressively increasing concentrations of levofloxacin and the levofloxacin-loaded nanoparticles. Mutations in quinolone resistance determining region (QRDR) of gyrA and parC and regulators of AcrAB efflux pump (soxR, soxS and acrR) for all the selected-mutants were determined using polymerase chain reaction and sequencing. Mutants developed upon exposure to the nanosized drug had higher sensitivity to levofloxacin, compared with the levofloxacin-selected mutants. In addition, mutations in gyrA were observed in the levofloxacin first mutants, but in the nanosized levofloxacin second mutants. In the third mutants, an additional mutation in parC and mutations in the regulators were found only in levofloxacin-selected mutants. Loading of levofloxacin…
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