Cell-type-independent infection dynamics of clinical Pseudomonas aeruginosa isolates in human airway epithelial models.
| Title: | Cell-type-independent infection dynamics of clinical Pseudomonas aeruginosa isolates in human airway epithelial models. |
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| Authors: | Colque CA; Department of Clinical Microbiology 9301, Rigshospitalet, 2100 Copenhagen Ø, Denmark. Electronic address: antcol@dtu.dk.; Lolle S; Department of Clinical Microbiology 9301, Rigshospitalet, 2100 Copenhagen Ø, Denmark.; La Rosa R; Department of Clinical Microbiology 9301, Rigshospitalet, 2100 Copenhagen Ø, Denmark; Department of Health Technology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark. Electronic address: rugros@dtu.dk.; Bendixen MP; Department of Clinical Microbiology 9301, Rigshospitalet, 2100 Copenhagen Ø, Denmark.; Rudjord-Levann AM; Department of Clinical Microbiology 9301, Rigshospitalet, 2100 Copenhagen Ø, Denmark.; Simões FB; Department of Clinical Microbiology 9301, Rigshospitalet, 2100 Copenhagen Ø, Denmark.; Aanæs K; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet, 2100 Copenhagen Ø, Denmark.; Molin S; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.; Johansen HK; Department of Clinical Microbiology 9301, Rigshospitalet, 2100 Copenhagen Ø, Denmark; Department of Health Technology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark. Electronic address: hkj@dtu.dk. |
| Source: | Cell reports [Cell Rep] 2026 Feb 24; Vol. 45 (2), pp. 116951. Date of Electronic Publication: 2026 Feb 09. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| MeSH Terms: | Pseudomonas aeruginosa*/pathogenicity ; Pseudomonas aeruginosa*/isolation & purification ; Pseudomonas aeruginosa*/genetics ; Pseudomonas Infections*/microbiology ; Pseudomonas Infections*/pathology ; Epithelial Cells*/microbiology ; Epithelial Cells*/pathology ; Respiratory Mucosa*/microbiology; Cystic Fibrosis/microbiology ; Cystic Fibrosis/pathology ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Humans ; Host-Pathogen Interactions ; Cell Line |
| Abstract: | Persistent bacterial infections pose major clinical challenges, particularly in people with cystic fibrosis (pwCF), in whom Pseudomonas aeruginosa can persist for decades despite antibiotic treatment. To investigate the host-pathogen interactions influencing infection outcomes, we modeled P. aeruginosa infection using human airway epithelial cells cultured at the air-liquid interface from both CF and non-CF donors and the BCi-NS1.1 cell line. Infection assays with reference and clinical strains revealed four distinct infection clusters based on virulence, epithelial damage, and localization, independent of model type or strain lineage. Correction of CF transmembrane conductance regulator protein (CFTR) channel function did not alter infection outcomes. Dual RNA sequencing showed conserved host inflammatory responses across models, while bacterial transcriptional profiles varied by host context, particularly in CF models. These findings demonstrate that while infection outcomes and host transcriptional responses are consistent across models, bacterial adaptation in the CF airways drives transcriptional reprogramming linked to persistence in pwCF.; (Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| Contributed Indexing: | Keywords: CP: microbiology; Pseudomonas aeruginosa; bacterial persistence; cystic fibrosis; host-pathogen interactions; infection models |
| Substance Nomenclature: | 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator) |
| Entry Date(s): | Date Created: 20260210 Date Completed: 20260307 Latest Revision: 20260307 |
| Update Code: | 20260307 |
| DOI: | 10.1016/j.celrep.2026.116951 |
| PMID: | 41666013 |
| Database: | MEDLINE |
Journal Article