title: Anionic fluoroquinolones as antibacterials against biofilm-producing Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is a common biofilm-forming bacterial pathogen implicated in diseases of the lungs. The extracellular polymeric substances (EPS) of respiratory Pseudomonas biofilms are largely comprised of anionic molecules such as rhamnolipids and alginate that promote a mucoid phenotype. In this Letter, we examine the ability of negatively-charged fluoroquinolones to transverse the EPS and inhibit the growth of mucoid P. aeruginosa. Anionic fluoroquinolones were further compared with standard antibiotics via a novel microdiffusion assay to evaluate drug penetration through pseudomonal alginate and respiratory mucus from a patient with cystic fibrosis.
authors.affiliation: Department 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. Electronic address: longt@marshall.edu.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Long
authors.affiliation: Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Lexie C
authors.initials: LC
authors.lastname: Keding
authors.affiliation: Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV 25755, United States.
authors.forename: Demetria D
authors.initials: DD
authors.lastname: Lewis
authors.affiliation: Department of Pediatrics, College of Medicine, University of Kentucky, Lexington, KY 40506, United States.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Anstead
authors.affiliation: Progenesis Technologies, LLC, Huntington, WV 25755, United States.
authors.forename: T Ryan
authors.initials: TR
authors.lastname: Withers
authors.affiliation: Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States; Department of Pediatrics, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States; Progenesis Technologies, LLC, Huntington, WV 25755, United States.
authors.forename: Hongwei D
authors.initials: HD
authors.lastname: Yu
mesh_terms: D000838:Anions / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000502:physiology*
chemical_list: D000838:Anions; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones
keywords: Antibacterial; Biofilm; Fluoroquinolone; Mucoid; Pseudomonas
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