{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:52:45Z","timestamp":1792086765300,"version":"4.4.0"},"reference-count":57,"publisher":"National Academy of Sciences","issue":"42","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["WHITEL20A0"],"award-info":[{"award-number":["WHITEL20A0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["WHITEL22G0"],"award-info":[{"award-number":["WHITEL22G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["LETIZI24G0-BASBAUM"],"award-info":[{"award-number":["LETIZI24G0-BASBAUM"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:p>\n                    Chronic lung infection with\n                    <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                    is a major complication of cystic fibrosis (CF), contributing to lung function decline and increased morbidity and mortality. Laboratory models are used to study CF infections, but their relevance depends on how accurately they reproduce microbial physiology during human infection. We previously developed a framework that uses bacterial gene expression in human infections to quantify model accuracy. Here, we applied this framework to determine how a major therapeutic intervention impacts\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    physiology in the lungs of people with CF (pwCF) and to develop and evaluate refined preclinical models. We focused on elexacaftor\/tezacaftor\/ivacaftor (ETI), a highly effective CFTR modulator therapy that has improved outcomes for pwCF. However, evidence indicates that\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    lung infections persist despite ETI therapy. Analysis of\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    transcriptomes from human sputum collected before and after ETI initiation revealed minimal changes in gene expression, indicating that the CF airway continues to support a similar bacterial transcriptional state despite therapy. We then evaluated how strain selection, zinc limitation, and polymicrobial coculture influence the ability of laboratory models to recapitulate\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    gene expression in human CF sputum. Growth of CF clinical isolates in zinc-limited synthetic CF sputum medium produced the most accurate model, whereas population-based cultures and coculture with\n                    <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                    had limited effects. These findings show that ETI therapy has little impact on the conserved\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    transcriptional state in human CF sputum and that refined sputum-like models remain useful for studying persistent infection in the postmodulator era.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2622466123","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:37:33Z","timestamp":1792085853000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["The impact of modulator therapy on the\n                    <i>Pseudomonas aeruginosa<\/i>\n                    cystic fibrosis lung transcriptome"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4795-6259","authenticated-orcid":false,"given":"Morgana","family":"Letizia","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01zkghx44","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences and Center for Microbial Dynamics and Infection, Georgia Institute of Technology","place":["Atlanta"]},{"name":"Emory-Children\u2019s Cystic Fibrosis Center","place":["Atlanta"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Whiteley","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01zkghx44","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences and Center for Microbial Dynamics and Infection, Georgia Institute of Technology","place":["Atlanta"]},{"name":"Emory-Children\u2019s Cystic Fibrosis Center","place":["Atlanta"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances L.","family":"Diggle","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01zkghx44","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences and Center for Microbial Dynamics and Infection, Georgia Institute of Technology","place":["Atlanta"]},{"name":"Emory-Children\u2019s Cystic Fibrosis Center","place":["Atlanta"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9242-689X","authenticated-orcid":false,"given":"Angela N.","family":"Davis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01zkghx44","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences and Center for Microbial Dynamics and Infection, Georgia Institute of Technology","place":["Atlanta"]},{"name":"Emory-Children\u2019s Cystic Fibrosis Center","place":["Atlanta"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Morgan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00cvxb145","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Washington School of Medicine","place":["Seattle"]},{"id":[{"id":"https:\/\/ror.org\/00cvxb145","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Washington School of Medicine","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Grogan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/029tkqm80","id-type":"ROR","asserted-by":"publisher"}],"name":"National Referral Center for Adult Cystic Fibrosis, National Referral Center for Adult Cystic Fibrosis, St. Vincent\u2019s University Hospital","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Baugh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05m7pjf47","id-type":"ROR","asserted-by":"publisher"}],"name":"University College Dublin School of Medicine","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward F.","family":"McKone","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/029tkqm80","id-type":"ROR","asserted-by":"publisher"}],"name":"National Referral Center for Adult Cystic Fibrosis, National Referral Center for Adult Cystic Fibrosis, St. Vincent\u2019s University Hospital","place":["Dublin, Ireland"]},{"id":[{"id":"https:\/\/ror.org\/05m7pjf47","id-type":"ROR","asserted-by":"publisher"}],"name":"University College Dublin School of Medicine","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep 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Deposited 12 May 2026.","journal-title":"NCBI Sequence Read Archive"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031092"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00749-15"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01603-15"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/apm.13234"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2622466123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:37:53Z","timestamp":1792085873000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2622466123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":57,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2026,10,20]]}},"alternative-id":["10.1073\/pnas.2622466123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2622466123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"2026-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2622466123"}}