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Kirklin Research\u00a0and\u00a0Education Foundation"],"award-info":[{"award-number":["John W. Kirklin Research\u00a0and\u00a0Education Foundation"]}],"id":[{"id":"10.13039\/100011221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["ROWE15R0 (to D.Y.C.)"],"award-info":[{"award-number":["ROWE15R0 (to D.Y.C.)"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010479","name":"Cook Medical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment.\n                      <jats:sc>l<\/jats:sc>\n                      \u2010Methionine is an amino acid with reported biofilm\u2010inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co\u2010treatment with ivacaftor and\n                      <jats:sc>l<\/jats:sc>\n                      \u2010methionine can reduce the formation of\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      biofilms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>P aeruginosa<\/jats:italic>\n                      (PAO\u20101 strain) biofilms were studied in the presence of\n                      <jats:sc>l<\/jats:sc>\n                      \u2010methionine and\/or ivacaftor. For static biofilm assays, PAO\u20101 was cultured in a 48\u2010well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live\/dead assays (BacTiter\u2010Glo\u2122 assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:sc>l<\/jats:sc>\n                      \u2010Methionine (0.5 \u03bcM) significantly reduced PAO\u20101 biofilm mass (32.4 \u00b1 18.0%; n = 4;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) compared with controls. Low doses of ivacaftor alone (4, 8, and 12 \u03bcg\/mL) had no effect on biofilm formation. When combined with ivacaftor (4 \u03bcg\/mL), a synergistic anti\u2010biofilm effect was noted at 0.05 \u03bcM and 0.5 \u03bcM of\n                      <jats:sc>l<\/jats:sc>\n                      \u2010methionine (two\u2010way analysis of variane,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0415) compared with corresponding concentrations of\n                      <jats:sc>l<\/jats:sc>\n                      \u2010methionine alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Ivacaftor enhanced the anti\u2010biofilm activity of\n                      <jats:sc>l<\/jats:sc>\n                      \u2010methionine against the PAO\u20101 strain of\n                      <jats:italic>P aeruginosa<\/jats:italic>\n                      . Further studies evaluating the efficacy of ivacaftor\/\n                      <jats:sc>l<\/jats:sc>\n                      \u2010methionine combinations for\n                      <jats:italic>P aeruginosa<\/jats:italic>\n                      sinusitis are planned.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alr.22088","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T11:22:42Z","timestamp":1518002562000},"page":"577-583","source":"Crossref","is-referenced-by-count":19,"title":["<scp>l<\/scp>\n                    \u2010Methionine anti\u2010biofilm activity against\n                    <i>Pseudomonas aeruginosa<\/i>\n                    is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor"],"prefix":"10.1002","volume":"8","author":[{"given":"Do\u2010Yeon","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center University of Alabama at Birmingham  Birmingham AL"},{"name":"Department of Biomedical Engineering University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Jin","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Mackey","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Weeks","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime A.","family":"Pe\u00f1a Garcia","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Skinner","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head &amp; 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