Anionic fluoroquinolones as antibacterials against biofilm-producing Pseudomonas aeruginosa

Timothy E Long1, Lexie C Keding2, Demetria D Lewis3

  • 1Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV 25755, United States; Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.

Insights

Negatively-charged fluoroquinolones show potential for penetrating Pseudomonas aeruginosa biofilms and inhibiting bacterial growth. This study compared their efficacy against standard antibiotics in cystic fibrosis mucus.

Area of Science:

  • Microbiology
  • Pharmacology
  • Biochemistry

Background:

  • Pseudomonas aeruginosa is a significant bacterial pathogen forming biofilms, particularly in lung infections.
  • Respiratory Pseudomonas biofilms contain anionic extracellular polymeric substances (EPS), like alginate and rhamnolipids, contributing to a mucoid phenotype.

Purpose of the Study:

  • To investigate the efficacy of anionic fluoroquinolones in penetrating Pseudomonas aeruginosa EPS.
  • To assess the growth inhibition of mucoid P. aeruginosa by anionic fluoroquinolones.
  • To compare the drug penetration of anionic fluoroquinolones with standard antibiotics.

Main Methods:

  • Utilized a novel microdiffusion assay.
  • Evaluated drug penetration through purified pseudomonal alginate.
  • Assessed drug penetration through respiratory mucus from cystic fibrosis patients.

Main Results:

  • Anionic fluoroquinolones demonstrated the ability to traverse the EPS layer of Pseudomonas biofilms.
  • The study provided comparative data on the penetration of anionic fluoroquinolones versus standard antibiotics.
  • Efficacy was tested in relevant models including patient-derived cystic fibrosis mucus.

Conclusions:

  • Anionic fluoroquinolones represent a promising therapeutic strategy for combating Pseudomonas aeruginosa biofilm infections.
  • The findings suggest potential for improved antibiotic delivery across challenging biofilm structures in respiratory diseases.

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