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Levofloxacin-Loaded Nanoparticles Decrease Emergence of Fluoroquinolone Resistance in Escherichia coli.

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Encapsulating levofloxacin in chitosan nanoparticles enhanced its antibacterial potency and significantly reduced the emergence of resistant bacterial mutants. This novel approach offers a promising strategy to combat antimicrobial resistance.

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Area of Science:

  • Microbiology
  • Nanotechnology
  • Pharmacology

Background:

  • Antimicrobial resistance (AMR) is a critical global health threat, diminishing the efficacy of existing antibacterial drugs.
  • Understanding the genetic basis of bacterial resistance is crucial for developing effective treatment strategies.

Purpose of the Study:

  • To encapsulate levofloxacin into chitosan (CS) nanoparticles.
  • To evaluate the antibacterial activity of levofloxacin-loaded CS nanoparticles.
  • To characterize genetic mutations conferring resistance to levofloxacin and its nanoparticle formulation in Escherichia coli.

Main Methods:

  • Stepwise selection of bacterial mutants upon exposure to increasing concentrations of free levofloxacin and levofloxacin-loaded CS nanoparticles.
  • Analysis of mutations in the quinolone resistance-determining region (QRDR) of gyrA and parC genes.
  • Investigation of mutations in regulators of the AcrAB efflux pump (soxR, soxS, acrR) using polymerase chain reaction and sequencing.

Main Results:

  • Mutants developed against levofloxacin-loaded nanoparticles exhibited higher sensitivity to levofloxacin compared to mutants selected with free levofloxacin.
  • Mutations in gyrA occurred earlier in mutants exposed to free levofloxacin than in those exposed to nanoparticle-encapsulated levofloxacin.
  • Emergence of resistance, including mutations in parC and efflux pump regulators, was significantly lower in bacteria exposed to levofloxacin-loaded nanoparticles.

Conclusions:

  • Loading levofloxacin into chitosan nanoparticles enhances its antibacterial efficacy.
  • Chitosan nanoparticle formulation of levofloxacin effectively reduces the emergence of resistant bacterial mutants.
  • This study is the first to demonstrate the role of antimicrobial-loaded nanoparticles in mitigating the development of bacterial resistance.