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The PA metabolite pyocyanin can induce senescence-associated \u03b2-galactosidase (SA-\u03b2gal), a lysosomal cell senescence marker. However, whether PA can induce cell senescence and therefore affect immune functions has not been studied. Using established airway epithelial culture models, we observed that PA infection increased SA-\u03b2gal activity and proinflammatory cytokines without increasing a comprehensive set of cell senescence markers. PA infection also resulted in lysosomal neutralization and decreased lysosome biogenesis, with the latter attenuated by rapamycin (RAPA), a senolytic and an established inhibitor of mTOR signaling. In conclusion, our study implies that PA infection does not induce cell senescence in the CF bronchial epithelium but disturbs lysosomal homeostasis, which can be attenuated by RAPA. These findings highlight lysosomal health as a promising therapeutic target in CF airways, especially as patients live longer yet remain susceptible to recurrent airway infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00347-26","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T13:52:50Z","timestamp":1782827570000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Pseudomonas aeruginosa<\/i>\n                    infection causes lysosomal dysfunction in the cystic fibrosis bronchial epithelium"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-7249","authenticated-orcid":true,"given":"Emma Lea","family":"Matthews","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan June","family":"Hirsch","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuen-You","family":"Tsai","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah J.","family":"McIntire-Ray","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana Acevedo","family":"Rua","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela N.","family":"Morales","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke I.","family":"Jones","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarrod W.","family":"Barnes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4610-182X","authenticated-orcid":true,"given":"Megan R.","family":"Kiedrowski","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-6768","authenticated-orcid":true,"given":"Stefanie","family":"Krick","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy & Critical Care Medicine, Heersink School of Medicine, The University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108387"},{"key":"e_1_3_4_3_2","unstructured":"Cystic Fibrosis Foundation. 2024. 2023 Annual data report. 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