Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways

Abstract 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 fatt...

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Autores principales:	Ariadna Fernández-Calvet, Irene Rodríguez-Arce, Goizeder Almagro, Javier Moleres, Begoña Euba, Lucía Caballero, Sara Martí, José Ramos-Vivas, Toby Leigh Bartholomew, Xabier Morales, Carlos Ortíz-de-Solórzano, José Enrique Yuste, José Antonio Bengoechea, Raquel Conde-Álvarez, Junkal Garmendia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/305eb8a34c7740f6a4bd2c713047f4de
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spelling	oai:doaj.org-article:305eb8a34c7740f6a4bd2c713047f4de2021-12-02T11:41:14ZModulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways10.1038/s41598-018-25232-y2045-2322https://doaj.org/article/305eb8a34c7740f6a4bd2c713047f4de2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25232-yhttps://doaj.org/toc/2045-2322Abstract 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.Ariadna Fernández-CalvetIrene Rodríguez-ArceGoizeder AlmagroJavier MoleresBegoña EubaLucía CaballeroSara MartíJosé Ramos-VivasToby Leigh BartholomewXabier MoralesCarlos Ortíz-de-SolórzanoJosé Enrique YusteJosé Antonio BengoecheaRaquel Conde-ÁlvarezJunkal GarmendiaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-17 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ariadna Fernández-Calvet Irene Rodríguez-Arce Goizeder Almagro Javier Moleres Begoña Euba Lucía Caballero Sara Martí José Ramos-Vivas Toby Leigh Bartholomew Xabier Morales Carlos Ortíz-de-Solórzano José Enrique Yuste José Antonio Bengoechea Raquel Conde-Álvarez Junkal Garmendia Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways
description	Abstract 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	article
author	Ariadna Fernández-Calvet Irene Rodríguez-Arce Goizeder Almagro Javier Moleres Begoña Euba Lucía Caballero Sara Martí José Ramos-Vivas Toby Leigh Bartholomew Xabier Morales Carlos Ortíz-de-Solórzano José Enrique Yuste José Antonio Bengoechea Raquel Conde-Álvarez Junkal Garmendia
author_facet	Ariadna Fernández-Calvet Irene Rodríguez-Arce Goizeder Almagro Javier Moleres Begoña Euba Lucía Caballero Sara Martí José Ramos-Vivas Toby Leigh Bartholomew Xabier Morales Carlos Ortíz-de-Solórzano José Enrique Yuste José Antonio Bengoechea Raquel Conde-Álvarez Junkal Garmendia
author_sort	Ariadna Fernández-Calvet
title	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_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_sort	modulation of haemophilus influenzae interaction with hydrophobic molecules by the vacj/mlaa lipoprotein impacts strongly on its interplay with the airways
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/305eb8a34c7740f6a4bd2c713047f4de
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Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways

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