Leah R Reznikov1, Mahmoud H Abou Alaiwa1, Cassie L Dohrn1, Nick D Gansemer1, Daniel J Diekema1, David A Stoltz1, Michael J Welsh2. 1. Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States. 2. Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States; Howard Hughes Medical Institute (HHMI), University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States. Electronic address: Michael-welsh@uiowa.edu.
Abstract
BACKGROUND: Ivacaftor increases CFTR channel activity and improves pulmonary function for individuals bearing a G551D mutation. Because ivacaftor structurally resembles quinolone antibiotics, we tested the hypothesis that ivacaftor possesses antibacterial properties. METHODS: Bioluminescence, colony forming unit, and minimal inhibitory concentration assays were used to assess viability of Staphylococcus aureus, Pseudomonas aeruginosa and multiple clinical microbial isolates. RESULTS: Ivacaftor induced a dose-dependent reduction in bioluminescence of S. aureus and decreased the number of colony forming units. We observed a similar but less robust effect in P. aeruginosa following outer membrane permeabilization. Ivacaftor inhibited the growth of respiratory isolates of S. aureus and Streptococcus pneumoniae and exhibited positive interactions with antibiotics against lab and respiratory strains of S. aureus and S. pneumoniae. CONCLUSION: These data indicate that ivacaftor exhibits antibacterial properties and raise the intriguing possibility that ivacaftor might have an antibiotic effect in people with CF.
BACKGROUND:Ivacaftor increases CFTR channel activity and improves pulmonary function for individuals bearing a G551D mutation. Because ivacaftor structurally resembles quinolone antibiotics, we tested the hypothesis that ivacaftor possesses antibacterial properties. METHODS: Bioluminescence, colony forming unit, and minimal inhibitory concentration assays were used to assess viability of Staphylococcus aureus, Pseudomonas aeruginosa and multiple clinical microbial isolates. RESULTS:Ivacaftor induced a dose-dependent reduction in bioluminescence of S. aureus and decreased the number of colony forming units. We observed a similar but less robust effect in P. aeruginosa following outer membrane permeabilization. Ivacaftor inhibited the growth of respiratory isolates of S. aureus and Streptococcus pneumoniae and exhibited positive interactions with antibiotics against lab and respiratory strains of S. aureus and S. pneumoniae. CONCLUSION: These data indicate that ivacaftor exhibits antibacterial properties and raise the intriguing possibility that ivacaftor might have an antibiotic effect in people with CF.
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