Persistence of Pseudomonas aeruginosa during ciprofloxacin therapy of a cystic fibrosis patient: transient resistance to quinolones and protein F-deficiency

J Antimicrob Chemother. 1990 Jun;25(6):995-1010. doi: 10.1093/jac/25.6.995.

Abstract

The mechanism of persistence was characterized in Pseudomonas aeruginosa isolates obtained ten days before (4405), on the tenth day of (4419), and four days after (4478) ciprofloxacin therapy in a cystic fibrosis patient. Isolate 4419 showed a 16-fold increase in resistance to ciprofloxacin, norfloxacin and nalidixic acid. The outer membrane of 4419 had no detectable protein F. A modified lipopolysaccharide profile, a longer lag phase before growth and a slower generation time were also noted for isolate 4419. Cell surface hydrophobicity was increased by 20% in 4419 whereas uptake of [14C]ciprofloxacin was equivalent in all three isolates. Ciprofloxacin doses causing 50% inhibition of DNA synthesis were proportional to MICs for each isolate indicating that the DNA gyrase of 4419 was resistant to quinolones. A quinolone-susceptible revertant of 4419 remained deficient in protein F. Protein F-deficiency was not associated with resistance to quinolones, nor to other antibiotics, supporting the view that it plays little role in outer membrane permeability to antibiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Infective Agents / pharmacology*
  • Antibodies, Monoclonal
  • Bacterial Outer Membrane Proteins / biosynthesis*
  • Chemical Phenomena
  • Chemistry, Physical
  • Ciprofloxacin / pharmacokinetics
  • Ciprofloxacin / therapeutic use*
  • Culture Media
  • Cystic Fibrosis / microbiology*
  • DNA Probes
  • DNA, Bacterial / analysis
  • DNA, Bacterial / biosynthesis
  • Drug Resistance, Microbial
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Lipopolysaccharides / isolation & purification
  • Male
  • Muscle Proteins / deficiency*
  • Phosphofructokinase-1, Muscle Type
  • Phosphofructokinases*
  • Proteins*
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics

Substances

  • Anti-Infective Agents
  • Antibodies, Monoclonal
  • Bacterial Outer Membrane Proteins
  • Culture Media
  • DNA Probes
  • DNA, Bacterial
  • Lipopolysaccharides
  • Muscle Proteins
  • Proteins
  • Ciprofloxacin
  • Phosphofructokinases
  • Phosphofructokinase-1, Muscle Type
  • PFKM protein, human