title: Antibacterial properties of the CFTR potentiator ivacaftor.
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.
  
  
  CONCLUSIONS
  These data indicate that ivacaftor exhibits antibacterial properties and raise the intriguing possibility that ivacaftor might have an antibiotic effect in people with CF.
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States.
authors.forename: Leah R
authors.initials: LR
authors.lastname: Reznikov
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States.
authors.forename: Mahmoud H
authors.initials: MH
authors.lastname: Abou Alaiwa
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States.
authors.forename: Cassie L
authors.initials: CL
authors.lastname: Dohrn
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States.
authors.forename: Nick D
authors.initials: ND
authors.lastname: Gansemer
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Diekema
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.affiliation: 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.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000627:Aminophenols / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D004357:Drug Synergism; D008163:Luminescent Measurements; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000627:Aminophenols; D000900:Anti-Bacterial Agents; C505032:CFTR protein, human; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: Antibiotic; Cystic fibrosis; Pseudomonas aeruginosa; Quinolone; Staphylococcus aureus