Chest
Laboratory and Animal InvestigationsEffects of Azithromycin on Clinical Isolates of Pseudomonas aeruginosa From Cystic Fibrosis Patients
Section snippets
Bacterial Strains and Culture Conditions
All strains were grown in Luria broth (LB) or M9 plus casamino acids.P aeruginosaPAO1 was used as a prototype. This strain has been sequenced and is generally used as the reference strain forP aeruginosagenetics. JP2 (PAO1lasIrhlI), a quorum-sensing mutant, has been previously described.14 A pyoverdin null mutant, PAO1pvdF, was obtained (M. Vasil, University of Colorado; Denver, CO)18 and was grown under selection as previously noted.P aeruginosaCIs 49, 63, and 78 were
Results The Effects of Azithromycin onP aeruginosaGrowth
The effect of clinically achievable amounts of azithromycin (approximately 2.5 to 5 μg/mL)5 on the growth rates of PAO1, a quorum-sensing mutant,lasIrhlI, a pyoverdin mutant,pvdF, and three CIs were compared (Fig 1). Azithromycin at a concentration of 5 μg/mL began to affect PAO1 growth at the end of the log phase and similarly inhibited the growth of the mutants lacking either quorum sensing genes or siderophore expression. The CIs behaved differently. All three were noted to be auxotrophs,
Discussion
There have been numerousin vitroandin vivostudies demonstrating that macrolide antibiotics have clinically useful effects in patients withP aeruginosapulmonary infection. Randomized, placebo-controlled studies 5 have indicated clinical improvement in CF patients receiving azithromycin without major adverse effects detected, as yet. In the studies reported herein, we have demonstrated that the effects of this macrolide antibiotic onP aeruginosaPAO1 protein synthesis may help to explain the
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This work was supported by the United States Cystic Fibrosis Foundation. Dr. Wagner was supported by a grant from Pfizer (Groton, CT)