دورية أكاديمية
Quorum-sensing inhibition abrogates the deleterious impact of Pseudomonas aeruginosa on airway epithelial repair.
| العنوان: | Quorum-sensing inhibition abrogates the deleterious impact of Pseudomonas aeruginosa on airway epithelial repair. |
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| المؤلفون: | Ruffin M; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada; Département de Médecine, Université de Montréal, Montréal, Québec, Canada;, Bilodeau C; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada; Département de Médecine, Université de Montréal, Montréal, Québec, Canada;, Maillé É; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada;, LaFayette SL; The Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University, Montréal, Québec, Canada., McKay GA; The Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University, Montréal, Québec, Canada., Trinh NT; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada; Département de Médecine, Université de Montréal, Montréal, Québec, Canada;, Beaudoin T; The Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University, Montréal, Québec, Canada., Desrosiers MY; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada;, Rousseau S; The Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University, Montréal, Québec, Canada., Nguyen D; The Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University, Montréal, Québec, Canada., Brochiero E; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada; Département de Médecine, Université de Montréal, Montréal, Québec, Canada; emmanuelle.brochiero@umontreal.ca. |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2016 Sep; Vol. 30 (9), pp. 3011-25. Date of Electronic Publication: 2016 May 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | Bacterial Proteins/*metabolism , Epithelial Cells/*microbiology , Pseudomonas aeruginosa/*physiology, Cell Movement ; Cell Proliferation ; Cells, Cultured ; Gene Expression Regulation, Bacterial/physiology ; Humans ; Mutation ; Respiratory Mucosa/cytology ; Respiratory System |
| مستخلص: | Chronic Pseudomonas aeruginosa lung infections are associated with progressive epithelial damage and lung function decline. In addition to its role in tissue injury, the persistent presence of P. aeruginosa-secreted products may also affect epithelial repair ability, raising the need for new antivirulence therapies. The purpose of our study was to better understand the outcomes of P. aeruginosa exoproducts exposure on airway epithelial repair processes to identify a strategy to counteract their deleterious effect. We found that P. aeruginosa exoproducts significantly decreased wound healing, migration, and proliferation rates, and impaired the ability of directional migration of primary non-cystic fibrosis (CF) human airway epithelial cells. Impact of exoproducts was inhibited after mutations in P. aeruginosa genes that encoded for the quorum-sensing (QS) transcriptional regulator, LasR, and the elastase, LasB, whereas impact was restored by LasB induction in ΔlasR mutants. P. aeruginosa purified elastase also induced a significant decrease in non-CF epithelial repair, whereas protease inhibition with phosphoramidon prevented the effect of P. aeruginosa exoproducts. Furthermore, treatment of P. aeruginosa cultures with 4-hydroxy-2,5-dimethyl-3(2H)-furanone, a QS inhibitor, abrogated the negative impact of P. aeruginosa exoproducts on airway epithelial repair. Finally, we confirmed our findings in human airway epithelial cells from patients with CF, a disease featuring P. aeruginosa chronic respiratory infection. These data demonstrate that secreted proteases under the control of the LasR QS system impair airway epithelial repair and that QS inhibitors could be of benefit to counteract the deleterious effect of P. aeruginosa in infected patients.-Ruffin, M., Bilodeau, C., Maillé, É., LaFayette, S. L., McKay, G. A., Trinh, N. T. N., Beaudoin, T., Desrosiers, M.-Y., Rousseau, S., Nguyen, D., Brochiero, E. Quorum-sensing inhibition abrogates the deleterious impact of Pseudomonas aeruginosa on airway epithelial repair. (© FASEB.) |
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| معلومات مُعتمدة: | Canada CIHR |
| فهرسة مساهمة: | Keywords: LasB elastase; LasR; cystic fibrosis; furanone QSI; infection |
| المشرفين على المادة: | 0 (Bacterial Proteins) |
| تواريخ الأحداث: | Date Created: 20160515 Date Completed: 20170822 Latest Revision: 20201209 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6191002 |
| DOI: | 10.1096/fj.201500166R |
| PMID: | 27178322 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
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| DOI: | 10.1096/fj.201500166R |