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oai:repisalud.isciii.es:20.500.12105/91472025-03-24T14:32:13Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16962col_20.500.12105_16970

00925njm 22002777a 4500 dc Fernández-Calvet, Ariadna author Rodríguez-Arce, Irene author Almagro, Goizeder author Moleres, Javier author Euba, Begoña author Caballero, Lucía author Martí, Sara author Ramos-Vivas, José author Bartholomew, Toby Leigh author Morales, Xabier author Ortíz-de-Solórzano, Carlos author Yuste, Jose Enrique author Bengoechea, Jose Antonio author Conde-Álvarez, Raquel author Garmendia, Junkal author 2018 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. Sci Rep. 2018 May 2;8(1):6872. 10.1038/s41598-018-25232-y 2045-2322 2045-2322 Scientific reports 29720703 http://hdl.handle.net/20.500.12105/9147 Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways