{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:49:03Z","timestamp":1791229743329,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1K08HL131867"],"award-info":[{"award-number":["1K08HL131867"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HL153079"],"award-info":[{"award-number":["1R01HL153079"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK072482"],"award-info":[{"award-number":["P30DK072482"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["ROWE19R0"],"award-info":[{"award-number":["ROWE19R0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["BIRKET20A0"],"award-info":[{"award-number":["BIRKET20A0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Ivacaftor exhibits anti-staphylococcal properties but does not clear Staphylococcus aureus from the lungs of people with cystic fibrosis (pwCF). We assessed whether exposure to therapeutic concentrations of ivacaftor could allow S. aureus to form small colony variants (SCVs), a phenotype commonly associated with bacterial persistence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Humanized G551D-CFTR (hG551D) rats were treated with ivacaftor for 7\u2005days. Concentrations in the plasma, epithelial lining fluid and lung tissue lysate were measured using LC-MS\/MS. Survival of S. aureus during ivacaftor treatment was assessed in an hG551D rat model of lung infection. S. aureus adaptation to therapeutic concentrations of ivacaftor was investigated in vitro by serial passage in the presence of 10\u2005\u00b5M ivacaftor. Bacterial survival in the presence of antimicrobials was evaluated using growth curves and density assays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Ivacaftor plasma concentrations of treated hG551D rats reached 3.488\u200a\u00b1\u200a1.118\u2005\u00b5M, with more variable concentrations in the epithelial lining fluid and lung tissue lysate. During S. aureus infection, ivacaftor-treated hG551D rats returned similar numbers of bacteria from the lung, compared with vehicle-treated controls. Exposure of S. aureus to ivacaftor in vitro led to the formation of ivacaftor-tolerant SCVs with an unstable phenotype and increased antibiotic tolerance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Treatment with ivacaftor did not alter S. aureus burden in the cystic fibrosis rat and led to the formation of tolerant SCVs in vitro, suggesting that development of an SCV phenotype may allow S. aureus to persist in the cystic fibrosis lung during ivacaftor therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jacamr\/dlae185","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T20:50:24Z","timestamp":1733863824000},"source":"Crossref","is-referenced-by-count":4,"title":["Evaluating the effects of ivacaftor exposure on <i>Staphylococcus aureus<\/i> small colony variant development and antibiotic 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnathan D","family":"Keith","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley M","family":"Oden","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander E","family":"Dowell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward P","family":"Acosta","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S","family":"Guimbellot","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]},{"name":"Department of Pediatrics, Division of Pediatric Pulmonary and Sleep Medicine, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan R","family":"Kiedrowski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-6596","authenticated-orcid":false,"given":"Susan E","family":"Birket","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham , Birmingham, AL 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