Dual RNA sequencing of a co-culture model of Pseudomonas aeruginosa and human 2D upper airway organoids
Abstract Pseudomonas aeruginosa is a Gram-negative bacterium that is notorious for airway infections in cystic fibrosis (CF) subjects. Bacterial quorum sensing (QS) coordinates virulence factor expression and biofilm formation at population level. Better understanding of QS in the bacterium-host int...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-82500-w |
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| author | Cayetano Pleguezuelos-Manzano Wouter A. G. Beenker Gijs J. F. van Son Harry Begthel Gimano D. Amatngalim Jeffrey M. Beekman Hans Clevers Jeroen den Hertog |
| author_facet | Cayetano Pleguezuelos-Manzano Wouter A. G. Beenker Gijs J. F. van Son Harry Begthel Gimano D. Amatngalim Jeffrey M. Beekman Hans Clevers Jeroen den Hertog |
| author_sort | Cayetano Pleguezuelos-Manzano |
| collection | DOAJ |
| description | Abstract Pseudomonas aeruginosa is a Gram-negative bacterium that is notorious for airway infections in cystic fibrosis (CF) subjects. Bacterial quorum sensing (QS) coordinates virulence factor expression and biofilm formation at population level. Better understanding of QS in the bacterium-host interaction is required. Here, we set up a new P. aeruginosa infection model, using 2D upper airway nasal organoids that were derived from 3D organoids. Using dual RNA-sequencing, we dissected the interaction between organoid epithelial cells and WT or QS-mutant P. aeruginosa strains. Since only a single healthy individual and a single CF subject were used as donors for the organoids, conclusions about CF-specific effects could not be deduced. However, P. aeruginosa induced epithelial inflammation, whereas QS signaling did not affect the epithelial airway cells. Conversely, the epithelium influenced infection-related processes of P. aeruginosa, including QS-mediated regulation. Comparison of our model with samples from the airways of CF subjects indicated that our model recapitulates important aspects of infection in vivo. Hence, the 2D airway organoid infection model is relevant and may help to reduce the future burden of P. aeruginosa infections in CF. |
| format | Article |
| id | doaj-art-dfae0fad6dc5453aaae4588f2ab1e7d0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-dfae0fad6dc5453aaae4588f2ab1e7d02025-01-19T12:24:31ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-024-82500-wDual RNA sequencing of a co-culture model of Pseudomonas aeruginosa and human 2D upper airway organoidsCayetano Pleguezuelos-Manzano0Wouter A. G. Beenker1Gijs J. F. van Son2Harry Begthel3Gimano D. Amatngalim4Jeffrey M. Beekman5Hans Clevers6Jeroen den Hertog7Hubrecht Institute-KNAW and University Medical Center UtrechtHubrecht Institute-KNAW and University Medical Center UtrechtOncode Institute, Hubrecht Institute-KNAW and University Medical CenterHubrecht Institute-KNAW and University Medical Center UtrechtDepartment of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNGDepartment of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNGHubrecht Institute-KNAW and University Medical Center UtrechtHubrecht Institute-KNAW and University Medical Center UtrechtAbstract Pseudomonas aeruginosa is a Gram-negative bacterium that is notorious for airway infections in cystic fibrosis (CF) subjects. Bacterial quorum sensing (QS) coordinates virulence factor expression and biofilm formation at population level. Better understanding of QS in the bacterium-host interaction is required. Here, we set up a new P. aeruginosa infection model, using 2D upper airway nasal organoids that were derived from 3D organoids. Using dual RNA-sequencing, we dissected the interaction between organoid epithelial cells and WT or QS-mutant P. aeruginosa strains. Since only a single healthy individual and a single CF subject were used as donors for the organoids, conclusions about CF-specific effects could not be deduced. However, P. aeruginosa induced epithelial inflammation, whereas QS signaling did not affect the epithelial airway cells. Conversely, the epithelium influenced infection-related processes of P. aeruginosa, including QS-mediated regulation. Comparison of our model with samples from the airways of CF subjects indicated that our model recapitulates important aspects of infection in vivo. Hence, the 2D airway organoid infection model is relevant and may help to reduce the future burden of P. aeruginosa infections in CF.https://doi.org/10.1038/s41598-024-82500-wAirway organoidsPseudomonas aeruginosa2D co-cultureInfection modelDual RNA-sequencingQuorum sensing |
| spellingShingle | Cayetano Pleguezuelos-Manzano Wouter A. G. Beenker Gijs J. F. van Son Harry Begthel Gimano D. Amatngalim Jeffrey M. Beekman Hans Clevers Jeroen den Hertog Dual RNA sequencing of a co-culture model of Pseudomonas aeruginosa and human 2D upper airway organoids Scientific Reports Airway organoids Pseudomonas aeruginosa 2D co-culture Infection model Dual RNA-sequencing Quorum sensing |
| title | Dual RNA sequencing of a co-culture model of Pseudomonas aeruginosa and human 2D upper airway organoids |
| title_full | Dual RNA sequencing of a co-culture model of Pseudomonas aeruginosa and human 2D upper airway organoids |
| title_fullStr | Dual RNA sequencing of a co-culture model of Pseudomonas aeruginosa and human 2D upper airway organoids |
| title_full_unstemmed | Dual RNA sequencing of a co-culture model of Pseudomonas aeruginosa and human 2D upper airway organoids |
| title_short | Dual RNA sequencing of a co-culture model of Pseudomonas aeruginosa and human 2D upper airway organoids |
| title_sort | dual rna sequencing of a co culture model of pseudomonas aeruginosa and human 2d upper airway organoids |
| topic | Airway organoids Pseudomonas aeruginosa 2D co-culture Infection model Dual RNA-sequencing Quorum sensing |
| url | https://doi.org/10.1038/s41598-024-82500-w |
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