[HTML][HTML] Antibacterial properties of the CFTR potentiator ivacaftor

LR Reznikov, MH Abou Alaiwa, CL Dohrn… - Journal of Cystic …, 2014 - Elsevier
LR Reznikov, MH Abou Alaiwa, CL Dohrn, ND Gansemer, DJ Diekema, DA Stoltz, MJ Welsh
Journal of Cystic Fibrosis, 2014Elsevier
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 …
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.
Elsevier