{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:21:55Z","timestamp":1790446915480,"version":"4.1.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":112,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000849","name":"NC3Rs","doi-asserted-by":"publisher","award":["NC\/S00100\/1"],"award-info":[{"award-number":["NC\/S00100\/1"]}],"id":[{"id":"10.13039\/501100000849","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Strategic Research Centre","award":["SRC 022"],"award-info":[{"award-number":["SRC 022"]}]},{"DOI":"10.13039\/501100000292","name":"UK Cystic Fibrosis Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"CF Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome and Royal Society Sir Henry Dale","award":["204457\/Z\/16\/Z"],"award-info":[{"award-number":["204457\/Z\/16\/Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pseudomonas aeruginosa is a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Prolonged infection allows the accumulation of mutations and horizontal gene transfer, increasing the likelihood of adaptive phenotypic traits. Adaptation is proposed to arise first in bacterial populations colonizing upper airway environments. Here, we model this process using an experimental evolution approach. Pseudomonas aeruginosa PAO1, which is not airway adapted, was serially passaged, separately, in media chemically reflective of upper or lower airway environments. To explore whether the CF environment selects for unique traits, we separately passaged PAO1 in airway-mimicking media with or without CF-specific factors. Our findings demonstrated that all airway environments\u2014sinus and lungs, under CF and non-CF conditions\u2014selected for loss of twitching motility, increased resistance to multiple antibiotic classes, and a hyper-biofilm phenotype. These traits conferred increased airway colonization potential in an in vivo model. CF-like conditions exerted stronger selective pressures, leading to emergence of more pronounced phenotypes. Loss of twitching was associated with mutations in type IV pili genes. Type IV pili mediate surface attachment, twitching, and induction of cAMP signalling. We additionally identified multiple evolutionary routes to increased biofilm formation involving regulation of cyclic-di-GMP signalling. These included the loss of function mutations in bifA and dipA phosphodiesterase genes and activating mutations in the siaA phosphatase. These data highlight that airway environments select for traits associated with sessile lifestyles and suggest upper airway niches support emergence of phenotypes that promote establishment of lung infection.<\/jats:p>","DOI":"10.1093\/ismejo\/wrae065","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T14:40:20Z","timestamp":1713796820000},"source":"Crossref","is-referenced-by-count":12,"title":["Secondary messenger signalling influences <i>Pseudomonas aeruginosa<\/i> adaptation to sinus and lung environments"],"prefix":"10.1093","volume":"18","author":[{"given":"Dilem","family":"Ruhluel","sequence":"first","affiliation":[{"name":"Department of Clinical Infection , Microbiology and Immunology, , Ronald Ross Building, 8 West Derby Street, Liverpool , United Kingdom"},{"name":"University of Liverpool , Microbiology and Immunology, , Ronald Ross Building, 8 West Derby Street, Liverpool , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"Fisher","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus , Cambridge , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E","family":"Barton","sequence":"additional","affiliation":[{"name":"Division of Molecular Microbiology, University of Dundee , Dow Street, Dundee , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hollie","family":"Leighton","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection , Microbiology and Immunology, , Ronald Ross Building, 8 West Derby Street, Liverpool , United Kingdom"},{"name":"University of Liverpool , Microbiology and Immunology, , Ronald Ross Building, 8 West Derby Street, Liverpool , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Molecular Microbiology, University of Dundee , Dow Street, Dundee , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Amores Morillo","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection , Microbiology and Immunology, , Ronald Ross Building, 8 West Derby Street, Liverpool , United Kingdom"},{"name":"University of Liverpool , Microbiology and Immunology, , Ronald Ross Building, 8 West Derby Street, Liverpool , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Microbiology , Moyne Institute of Preventive Medicine, , Dublin, 2 , Ireland"},{"name":"Trinity College , Moyne Institute of Preventive Medicine, , Dublin, 2 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne L","family":"Fothergill","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection , Microbiology and Immunology, , Ronald Ross Building, 8 West Derby Street, Liverpool , United Kingdom"},{"name":"University of Liverpool , Microbiology and Immunology, , Ronald Ross Building, 8 West Derby Street, Liverpool , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R","family":"Neill","sequence":"additional","affiliation":[{"name":"Division of Molecular Microbiology, University of Dundee , Dow Street, Dundee , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"2024051815361466100_ref1","doi-asserted-by":"crossref","first-page":"1602108","DOI":"10.1183\/13993003.02108-2016","article-title":"Pseudomonas aeruginosa adaptation and diversification in the non-cystic fibrosis bronchiectasis lung","volume":"49","author":"Hilliam","year":"2017","journal-title":"Eur Respir J"},{"key":"2024051815361466100_ref2","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41579-020-00477-5","article-title":"Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis","volume":"19","author":"Rossi","year":"2021","journal-title":"Nat Rev Microbiol"},{"key":"2024051815361466100_ref3","doi-asserted-by":"crossref","first-page":"665759","DOI":"10.3389\/fcimb.2021.665759","article-title":"The building blocks of antimicrobial resistance in Pseudomonas aeruginosa: implications for current resistance-breaking therapies","volume":"11","author":"Langendonk","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"2024051815361466100_ref4","first-page":"mgen000511","article-title":"Transmission, adaptation and geographical spread of the Pseudomonas aeruginosa Liverpool epidemic strain","volume":"7","author":"Moore","year":"2021","journal-title":"Microb Genom"},{"key":"2024051815361466100_ref5","first-page":"000681","article-title":"Genome evolution drives transcriptomic and phenotypic adaptation in Pseudomonas aeruginosa during 20 years of infection","volume":"7","author":"Wardell","year":"2021","journal-title":"Microb Genom"},{"key":"2024051815361466100_ref6","doi-asserted-by":"crossref","first-page":"106285","DOI":"10.1016\/j.rmed.2020.106285","article-title":"Pseudomonas aeruginosa associated with severity of non-cystic fibrosis bronchiectasis measured by the modified bronchiectasis severity score (BSI) and the FACED: the US bronchiectasis and NTM research registry (BRR) study","volume":"177","author":"Choate","year":"2021","journal-title":"Respir Med"},{"key":"2024051815361466100_ref7","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.cmi.2019.06.011","article-title":"Pseudomonas aeruginosa and risk of death and exacerbations in patients with chronic obstructive pulmonary disease: an observational cohort study of 22 053 patients","volume":"26","author":"Eklof","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"2024051815361466100_ref8","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1099\/mic.0.000393","article-title":"Virulence adaptations of Pseudomonas aeruginosa isolated from patients with non-cystic fibrosis bronchiectasis","volume":"162","author":"Woo","year":"2016","journal-title":"Microbiology (Reading)."},{"key":"2024051815361466100_ref9","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.cmi.2022.01.017","article-title":"Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease","volume":"28","author":"Eklof","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"2024051815361466100_ref10","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/molbev\/msaa226","article-title":"Evolutionary genomics 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