Antibacterial properties of the CFTR potentiator ivacaftor

BackgroundIvacaftor 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.MethodsBioluminescence, colony forming unit, and minimal inhibitory concentration assays were used to assess viability of Staphylococcus aureus, Pseudomonas aeruginosa and multiple clinical microbial isolates.ResultsIvacaftor 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.ConclusionThese data indicate that ivacaftor exhibits antibacterial properties and raise the intriguing possibility that ivacaftor might have an antibiotic effect in people with CF.