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

doi:10.1016/j.jcf.2014.02.004

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Antibacterial properties of the CFTR potentiator ivacaftor

Journal article

Open access

Peer reviewed

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 and Michael J Welsh

Journal of cystic fibrosis, Vol.13(5), pp.515-519

09/2014

DOI: 10.1016/j.jcf.2014.02.004

PMCID: PMC4718582

PMID: 24618508

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Abstract

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

Pseudomonas aeruginosa

Cystic fibrosis

Antibiotic

Quinolone

Staphylococcus aureus

Details

Title: Subtitle: Antibacterial properties of the CFTR potentiator ivacaftor
Creators: Leah R Reznikov - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States
Mahmoud H Abou Alaiwa - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States
Cassie L Dohrn - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States
Nick D Gansemer - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States
Daniel J Diekema - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States
David A Stoltz - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States
Michael J Welsh - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States
Resource Type: Journal article
Publication Details: Journal of cystic fibrosis, Vol.13(5), pp.515-519
Publisher: Elsevier B.V
DOI: 10.1016/j.jcf.2014.02.004
PMID: 24618508
PMCID: PMC4718582
ISSN: 1569-1993
eISSN: 1873-5010
Grant note: name: NIH Cardiovascular Interdisciplinary Research Fellowship, award: HL007121; name: NIH, award: HL091842; DOI: 10.13039/100000897, name: Cystic Fibrosis Foundation, award: R458
Language: English
Date published: 09/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Infectious Diseases; Pathology; Neurosurgery; Internal Medicine
Record Identifier: 9983986375702771

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