Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways
Airway infection by nontypeable Haemophilus influenzae (NTHi) associates to chronic obstructive pulmonary disease (COPD) exacerbation and asthma neutrophilic airway inflammation. Lipids are key inflammatory mediators in these disease conditions and consequently, NTHi may encounter free fatty acids d...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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Nature
2023
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| Online Access: | https://hdl.handle.net/10171/65543 |
| _version_ | 1793400401218764800 |
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| author | Fernández-Calvet, A. (Ariadna) Rodríguez-Arce, I. (Irene) Almagro, G. (Goizeder) Moleres, J. (Javier) Euba, B. (Begoña) Caballero, L. (Lucía) Martí, S. (Sara) Ramos-Vivas, J. (Jose) Leigh-Bartholomew, T. (Toby) Morales-Urteaga, X. (Xabier) Ortiz-de-Solorzano, C. (Carlos) Yuste, J.E. (José Enrique) Bengoechea, J.A. (José A.) Conde-Alvarez, R. (Raquel) Garmendia, J. (Junkal) |
| author_facet | Fernández-Calvet, A. (Ariadna) Rodríguez-Arce, I. (Irene) Almagro, G. (Goizeder) Moleres, J. (Javier) Euba, B. (Begoña) Caballero, L. (Lucía) Martí, S. (Sara) Ramos-Vivas, J. (Jose) Leigh-Bartholomew, T. (Toby) Morales-Urteaga, X. (Xabier) Ortiz-de-Solorzano, C. (Carlos) Yuste, J.E. (José Enrique) Bengoechea, J.A. (José A.) Conde-Alvarez, R. (Raquel) Garmendia, J. (Junkal) |
| author_sort | Fernández-Calvet, A. (Ariadna) |
| collection | DSpace |
| description | Airway infection by nontypeable Haemophilus influenzae (NTHi) associates to chronic obstructive pulmonary disease (COPD) exacerbation and asthma neutrophilic airway inflammation. Lipids are key inflammatory mediators in these disease conditions and consequently, NTHi may encounter free fatty acids during airway persistence. However, molecular information on the interplay NTHi-free fatty acids is limited, and we lack evidence on the importance of such interaction to infection. Maintenance of the outer membrane lipid asymmetry may play an essential role in NTHi barrier function and interaction with hydrophobic molecules. VacJ/MlaA-MlaBCDEF prevents phospholipid accumulation at the bacterial surface, being the only system involved in maintaining membrane asymmetry identified in NTHi. We assessed the relationship among the NTHi VacJ/MlaA outer membrane lipoprotein, bacterial and exogenous fatty acids, and respiratory infection. The vacJ/mlaA gene inactivation increased NTHi fatty acid and phospholipid global content and fatty acyl specific species, which in turn increased bacterial susceptibility to hydrophobic antimicrobials, decreased NTHi epithelial infection, and increased clearance during pulmonary infection in mice with both normal lung function and emphysema, maybe related to their shared lung fatty acid profiles. Altogether, we provide evidence for VacJ/MlaA as a key bacterial factor modulating NTHi survival at the human airway upon exposure to hydrophobic molecules. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-65543 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2023 |
| publisher | Nature |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-655432024-02-08T10:43:58Z Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways Fernández-Calvet, A. (Ariadna) Rodríguez-Arce, I. (Irene) Almagro, G. (Goizeder) Moleres, J. (Javier) Euba, B. (Begoña) Caballero, L. (Lucía) Martí, S. (Sara) Ramos-Vivas, J. (Jose) Leigh-Bartholomew, T. (Toby) Morales-Urteaga, X. (Xabier) Ortiz-de-Solorzano, C. (Carlos) Yuste, J.E. (José Enrique) Bengoechea, J.A. (José A.) Conde-Alvarez, R. (Raquel) Garmendia, J. (Junkal) Notypeable haemophilus influenzae (NTHi) Chronic obstructive pulmonary disease (COPD) Asthma neutrophilic airway inflammation Airway infection by nontypeable Haemophilus influenzae (NTHi) associates to chronic obstructive pulmonary disease (COPD) exacerbation and asthma neutrophilic airway inflammation. Lipids are key inflammatory mediators in these disease conditions and consequently, NTHi may encounter free fatty acids during airway persistence. However, molecular information on the interplay NTHi-free fatty acids is limited, and we lack evidence on the importance of such interaction to infection. Maintenance of the outer membrane lipid asymmetry may play an essential role in NTHi barrier function and interaction with hydrophobic molecules. VacJ/MlaA-MlaBCDEF prevents phospholipid accumulation at the bacterial surface, being the only system involved in maintaining membrane asymmetry identified in NTHi. We assessed the relationship among the NTHi VacJ/MlaA outer membrane lipoprotein, bacterial and exogenous fatty acids, and respiratory infection. The vacJ/mlaA gene inactivation increased NTHi fatty acid and phospholipid global content and fatty acyl specific species, which in turn increased bacterial susceptibility to hydrophobic antimicrobials, decreased NTHi epithelial infection, and increased clearance during pulmonary infection in mice with both normal lung function and emphysema, maybe related to their shared lung fatty acid profiles. Altogether, we provide evidence for VacJ/MlaA as a key bacterial factor modulating NTHi survival at the human airway upon exposure to hydrophobic molecules. 2023-02-23T15:42:48Z 2023-02-23T15:42:48Z 2018 info:eu-repo/semantics/article https://hdl.handle.net/10171/65543 eng info:eu-repo/grantAgreement/MINECO/Ayudas para contratos predoctorales para la formación de doctores 2013/BES-2013- 062644/ES/BES-2013- 062644 info:eu-repo/grantAgreement/MINECO/Proyectos de Investigación Fundamental No-Orientada/SAF2012-31166/ES/IMPLICACION DE FUNCIONES DEL HUESPED, FACTORES DE VIRULENCIA BACTERIANOS, E INTERFERENCIA TERAPEUTICA EN LA INFECCION POR EL PATOGENO RESPIRATORIO HAEMOPHILUS INFLUENZAE info:eu-repo/grantAgreement/MINECO/Proyectos de I+D+I dentro del Programa Estatal Retos de la Sociedad (2015)/ SAF2015-66520-R/ES/ADAPTACION EVOLUTIVA, PATOGENESIS Y SUBVERSION EUCARIOTA POR HAEMOPHILUS INFLUENZAE EN EL PULMON EPOC: IDENTIFICACION, CARACTERIZACION Y VALORACION DE ESTRATEGIAS TERAPEUTICAS info:eu-repo/grantAgreement/MINECO/Proyectos de I+D+I dentro del Programa Estatal Retos de la Sociedad (2015)/DPI2015-64221/ES/DISEÑO Y FABRICACION DE DISPOSITIVOS MICROFLUIDICOS PARA EL ESTUDIO MEDIANTE ANALISIS DE IMAGEN Y MODELOS NUMERICOS DE LA MECANICA DE LA EXTRAVASACION TUMORAL info:eu-repo/semantics/openAccess application/pdf Nature |
| spellingShingle | Notypeable haemophilus influenzae (NTHi) Chronic obstructive pulmonary disease (COPD) Asthma neutrophilic airway inflammation Fernández-Calvet, A. (Ariadna) Rodríguez-Arce, I. (Irene) Almagro, G. (Goizeder) Moleres, J. (Javier) Euba, B. (Begoña) Caballero, L. (Lucía) Martí, S. (Sara) Ramos-Vivas, J. (Jose) Leigh-Bartholomew, T. (Toby) Morales-Urteaga, X. (Xabier) Ortiz-de-Solorzano, C. (Carlos) Yuste, J.E. (José Enrique) Bengoechea, J.A. (José A.) Conde-Alvarez, R. (Raquel) Garmendia, J. (Junkal) Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways |
| title | Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways |
| title_full | Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways |
| title_fullStr | Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways |
| title_full_unstemmed | Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways |
| title_short | Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways |
| title_sort | modulation of haemophilus influenzae interaction with hydrophobic molecules by the vacj/mlaa lipoprotein impacts strongly on its interplay with the airways |
| topic | Notypeable haemophilus influenzae (NTHi) Chronic obstructive pulmonary disease (COPD) Asthma neutrophilic airway inflammation |
| url | https://hdl.handle.net/10171/65543 |
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