Corticosteroids modulate biofilm formation and virulence of Pseudomonas aeruginosa

Corticosteroids are anti-inflammatory drugs commonly administered to patients with chronic obstructive pulmonary disease (COPD), cystic fibrosis and similar lung pathologies, in which persistent infections with Pseudomonas aeruginosa are frequent. However, their therapeutic value is debatable becaus...

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Main Authors: Elena Jordana-Lluch, María Escobar-Salom, Gabriel Torrens, Isabel María Barceló, Miguel Ángel Estévez, Alex González-Alsina, Amanda Iglesias, Pere Joan Pont-Antona, María D. Macià, Sebastián Albertí, Paul Williams, Borja G. Cosío, Carlos Juan, Antonio Oliver
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Biofilm
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590207525000371
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author Elena Jordana-Lluch
María Escobar-Salom
Gabriel Torrens
Isabel María Barceló
Miguel Ángel Estévez
Alex González-Alsina
Amanda Iglesias
Pere Joan Pont-Antona
María D. Macià
Sebastián Albertí
Paul Williams
Borja G. Cosío
Carlos Juan
Antonio Oliver
author_facet Elena Jordana-Lluch
María Escobar-Salom
Gabriel Torrens
Isabel María Barceló
Miguel Ángel Estévez
Alex González-Alsina
Amanda Iglesias
Pere Joan Pont-Antona
María D. Macià
Sebastián Albertí
Paul Williams
Borja G. Cosío
Carlos Juan
Antonio Oliver
author_sort Elena Jordana-Lluch
collection DOAJ
description Corticosteroids are anti-inflammatory drugs commonly administered to patients with chronic obstructive pulmonary disease (COPD), cystic fibrosis and similar lung pathologies, in which persistent infections with Pseudomonas aeruginosa are frequent. However, their therapeutic value is debatable because of their adverse impact on host immunity. The aim of this work was to determine the impact of budesonide and fluticasone propionate on P. aeruginosa biology. We found that these corticosteroids attenuated its intrinsic pro-inflammatory properties (reduction of IL-8 release compared to controls ca. 15 % (budesonide) and 50 % (fluticasone propionate)) and cellular invasiveness (25 % and 40 % respectively). Corticosteroids enhanced P. aeruginosa biofilm formation in a time/dose-dependent manner (around 1.6-fold for the highest concentration, with this increase occurring more readily in sputum media)) and stimulated the release of extracellular DNA (2-fold increase), a key component of the biofilm matrix. Regarding the mechanisms involved, our results suggest that corticosteroids diffuse through P. aeruginosa's membrane influencing its fluidity and triggering cell envelope stress signalling pathways, as shown by an initial increase in mucA (σ22 regulon) expression, outer membrane vesicle release and accumulation of cyclic diguanylate (c-di-GMP). Changes in the levels of this intracellular signalling molecule, responsible for the switch from planktonic to biofilm lifestyle, may explain some of the phenotypes observed. In conclusion, our data, first obtained with type strains and proved to be reproducible when using COPD clinical isolates, suggest that corticosteroids could mediate a faster acquisition of the phenotypic characteristics associated with P. aeruginosa long-term adaptation to the chronic lung niche without undergoing mutation.
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spelling doaj-art-82e2c095eb5d4d9288b3558dc316481d2025-08-20T02:05:13ZengElsevierBiofilm2590-20752025-06-01910028910.1016/j.bioflm.2025.100289Corticosteroids modulate biofilm formation and virulence of Pseudomonas aeruginosaElena Jordana-Lluch0María Escobar-Salom1Gabriel Torrens2Isabel María Barceló3Miguel Ángel Estévez4Alex González-Alsina5Amanda Iglesias6Pere Joan Pont-Antona7María D. Macià8Sebastián Albertí9Paul Williams10Borja G. Cosío11Carlos Juan12Antonio Oliver13Health Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Microbiology Department, University Hospital Son Espases, 07010, Palma, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC), 28029, Madrid, Spain; Corresponding author Health Research Institute of the Balearic Islands (IdISBa), 07010, Palma, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Microbiology Department, University Hospital Son Espases, 07010, Palma, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC), 28029, Madrid, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Microbiology Department, University Hospital Son Espases, 07010, Palma, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Microbiology Department, University Hospital Son Espases, 07010, Palma, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC), 28029, Madrid, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Microbiology Department, University Hospital Son Espases, 07010, Palma, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122, Palma de Mallorca, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III (CIBERES), 28029, Madrid, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Microbiology Department, University Hospital Son Espases, 07010, Palma, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC), 28029, Madrid, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122, Palma de Mallorca, SpainBiodiscovery Institute and School of Life Sciences, University Park, University of Nottingham, Nottingham, NG7 2RD, United KingdomHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III (CIBERES), 28029, Madrid, Spain; Department of Respiratory Medicine, University Hospital Son Espases, 07010, Palma, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Microbiology Department, University Hospital Son Espases, 07010, Palma, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC), 28029, Madrid, Spain; Corresponding author. Health Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain.Health Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain; Microbiology Department, University Hospital Son Espases, 07010, Palma, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC), 28029, Madrid, SpainCorticosteroids are anti-inflammatory drugs commonly administered to patients with chronic obstructive pulmonary disease (COPD), cystic fibrosis and similar lung pathologies, in which persistent infections with Pseudomonas aeruginosa are frequent. However, their therapeutic value is debatable because of their adverse impact on host immunity. The aim of this work was to determine the impact of budesonide and fluticasone propionate on P. aeruginosa biology. We found that these corticosteroids attenuated its intrinsic pro-inflammatory properties (reduction of IL-8 release compared to controls ca. 15 % (budesonide) and 50 % (fluticasone propionate)) and cellular invasiveness (25 % and 40 % respectively). Corticosteroids enhanced P. aeruginosa biofilm formation in a time/dose-dependent manner (around 1.6-fold for the highest concentration, with this increase occurring more readily in sputum media)) and stimulated the release of extracellular DNA (2-fold increase), a key component of the biofilm matrix. Regarding the mechanisms involved, our results suggest that corticosteroids diffuse through P. aeruginosa's membrane influencing its fluidity and triggering cell envelope stress signalling pathways, as shown by an initial increase in mucA (σ22 regulon) expression, outer membrane vesicle release and accumulation of cyclic diguanylate (c-di-GMP). Changes in the levels of this intracellular signalling molecule, responsible for the switch from planktonic to biofilm lifestyle, may explain some of the phenotypes observed. In conclusion, our data, first obtained with type strains and proved to be reproducible when using COPD clinical isolates, suggest that corticosteroids could mediate a faster acquisition of the phenotypic characteristics associated with P. aeruginosa long-term adaptation to the chronic lung niche without undergoing mutation.http://www.sciencedirect.com/science/article/pii/S2590207525000371Pseudomonas aeruginosaChronic obstructive pulmonary diseaseCystic fibrosisBiofilmCorticosteroidsBudesonide
spellingShingle Elena Jordana-Lluch
María Escobar-Salom
Gabriel Torrens
Isabel María Barceló
Miguel Ángel Estévez
Alex González-Alsina
Amanda Iglesias
Pere Joan Pont-Antona
María D. Macià
Sebastián Albertí
Paul Williams
Borja G. Cosío
Carlos Juan
Antonio Oliver
Corticosteroids modulate biofilm formation and virulence of Pseudomonas aeruginosa
Biofilm
Pseudomonas aeruginosa
Chronic obstructive pulmonary disease
Cystic fibrosis
Biofilm
Corticosteroids
Budesonide
title Corticosteroids modulate biofilm formation and virulence of Pseudomonas aeruginosa
title_full Corticosteroids modulate biofilm formation and virulence of Pseudomonas aeruginosa
title_fullStr Corticosteroids modulate biofilm formation and virulence of Pseudomonas aeruginosa
title_full_unstemmed Corticosteroids modulate biofilm formation and virulence of Pseudomonas aeruginosa
title_short Corticosteroids modulate biofilm formation and virulence of Pseudomonas aeruginosa
title_sort corticosteroids modulate biofilm formation and virulence of pseudomonas aeruginosa
topic Pseudomonas aeruginosa
Chronic obstructive pulmonary disease
Cystic fibrosis
Biofilm
Corticosteroids
Budesonide
url http://www.sciencedirect.com/science/article/pii/S2590207525000371
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