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 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.

Bibliographic Details

Main Authors:	Fernández-Calvet, Ariadna, Rodríguez-Arce, Irene, Almagro, Goizeder, Moleres, Javier, Euba, Begoña, Caballero, Lucía, Martí, Sara, Ramos-Vivas, José, Bartholomew, Toby Leigh, Morales, Xabier, Ortiz-de-Solorzano, Carlos, Yuste, José, Bengoechea, José Antonio, Conde Álvarez, Raquel, Garmendia, Juncal
Other Authors:	Ministerio de Economía y Competitividad (España)
Format:	artículo biblioteca
Language:	English
Published:	Springer Nature 2018
Online Access:	http://hdl.handle.net/10261/191688 http://dx.doi.org/10.13039/501100007680 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/100008303 http://dx.doi.org/10.13039/501100003329
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