1. Antibacterial properties of the CFTR potentiator ivacaftor
Leah R. Reznikov, Mahmoud H. Abou Alaiwa, Cassie L. Dohrn, Nick D. Gansemer, Daniel J. Diekema, David A. Stoltz, Michael J. Welsh 
Journal of Cystic Fibrosis 
Volume 13, Issue 5, Pages (September 2014)
DOI: /j.jcf
Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions

2. Fig. 1
Antibacterial properties of ivacaftor. A) Ivacaftor induced a dose-dependent reduction in bioluminescence of S. aureus; n=8. B) Dose response of ivacaftor (n=8), vancomycin (n=4) and vancomycin+1μg/ml ivacaftor (n=4) at 30min. Data are normalized to vehicle controls; *P≤0.05 compared to vancomycin only. C) Incubation of S. aureus with ivacaftor (iva), vancomycin (vanc.) or vancomycin+1μg/ml ivacaftor (iva+vanc.) for 120min resulted in a reduction in the number of CFUs. The number following the label indicates the dose in μg/ml; n=4 experiments; *P≤0.05 compared to vancomycin (0.07μg/ml), # compared to ivacaftor (1μg/ml). D) Ivacaftor induced a dose-dependent reduction in bioluminescence of P. aeruginosa permeabilized with 0.2mM EDTA; n=5 experiments. E) Dose response of ivacaftor (n=5 experiments), ciprofloxacin (n=3 experiments) and ciprofloxacin+1μg/ml ivacaftor (n=3 experiments) at 60min. *P≤0.05 compared to ciprofloxacin only. Data are normalized to vehicle controls. F) Incubation of P. aeruginosa with ivacaftor (iva), ciprofloxacin (cip.) or ciprofloxacin+1μg/ml ivacaftor (iva+cip.) for 120min reduced the number of CFUs. The number following the label indicates the dose in μg/ml. For vehicle, n=5; ivacaftor 1μg/ml, n=4; ivacaftor 32μg/ml, n=5; ciprofloxacin μg/ml, n=3; ciprofloxacin 32μg/ml, n=3. Because in permeabilized P. aeruginosa, even very low doses of ciprofloxacin markedly decreased CFUs, we do not report the combination of ivacaftor and ciprofloxacin.
Journal of Cystic Fibrosis  , DOI: ( /j.jcf )
Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions

3. Supplemental Fig. 1
Lack of effect of ivacaftor on non-permeabilized P. aeruginosa. A) Ivacaftor failed to induce a dose-dependent reduction in bioluminescence of non-permeabilized P. aeruginosa (n=6 experiments). B) Dose response of ivacaftor (n=6 experiments), ciprofloxacin (n=3 experiments) and ciprofloxacin+1μg/ml ivacaftor (n=3 experiments) at 60min. A minimal effect of ivacaftor was observed. Consistent with this, no positive interactions of ciprofloxacin and ivacaftor were noted. Data are normalized to vehicle controls. C) Effect of incubation of P. aeruginosa with ivacaftor (iva), ciprofloxacin (cip.) or ciprofloxacin+1μg/ml ivacaftor (iva+cip.) for 120min on the number of CFUs; only ciprofloxacin at a dose of 32μg/ml had a robust effect. The number following the label indicates the dose in μg/ml. For vehicle, n=3; ivacaftor 1μg/ml, n=3; ivacaftor 32μg/ml, n=3; ciprofloxacin μg/ml, n=3; ciprofloxacin 32μg/ml, n=3.
Journal of Cystic Fibrosis  , DOI: ( /j.jcf )
Copyright © 2014 European Cystic Fibrosis Society. Terms and Conditions