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

Fernández Calvet, Ariadna; Rodríguez Arce, Irene; Almagro Zabalza, Goizeder; Moleres Apilluelo, Javier; Caballero Coronado, Lucía; Garmendia García, Juncal

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

dc.contributor.author	Fernández Calvet, Ariadna
dc.contributor.author	Rodríguez Arce, Irene
dc.contributor.author	Almagro Zabalza, Goizeder
dc.contributor.author	Moleres Apilluelo, Javier
dc.contributor.author	Caballero Coronado, Lucía
dc.contributor.author	Garmendia García, Juncal
dc.contributor.department	IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua	es_ES
dc.contributor.funder	Gobierno de Navarra / Nafarroako Gobernua, 03/2016	es
dc.contributor.funder	Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa	es
dc.date.accessioned	2020-11-12T13:59:56Z
dc.date.available	2020-11-12T13:59:56Z
dc.date.issued	2018
dc.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.	en
dc.description.sponsorship	A.F.C was funded by a contract from Ministerio Economía y Competitividad-MINECO, reference 20132RC947, Spain; I.R.A. is funded by a PhD studentship from Universidad Pública de Navarra, Spain; J.M. was funded by PhD studentship BES-2013-062644 from MINECO; S.M. is funded by a postdoctoral contract from CIBERES; L.C. was funded by a contract from MINECO, reference CS_NAV_IDAB_005, Spain; T.L.B. is the recipient of a PhD fellowship funded by the Department for Employment and Learning (Northern Ireland, UK). This work has been funded by grants from MINECO SAF2012-31166 and SAF2015-66520-R, from Health Department, Regional Govern from Navarra, Spain, reference 03/2016, and from SEPAR 31/2015 to J.G.; and by grant from MINECO DPI2015-64221 to COdS. CIBER is an initiative from Instituto de Salud Carlos III (ISCIII), Madrid, Spain.	en
dc.format.extent	17 p.
dc.format.mimetype	application/pdf	en
dc.identifier.doi	10.1038/s41598-018-25232-y
dc.identifier.issn	2045-2322
dc.identifier.uri	https://academica-e.unavarra.es/handle/2454/38649
dc.language.iso	eng	en
dc.publisher	Springer	en
dc.relation.ispartof	Scientific Reports, 2018, 8, 6872	en
dc.relation.projectID	info:eu-repo/grantAgreement/MINECO//SAF2012-31166/ES/	en
dc.relation.projectID	info:eu-repo/grantAgreement/MINECO//SAF2015-66520-R/ES/	en
dc.relation.projectID	info:eu-repo/grantAgreement/MINECO//DPI2015-64221-C2-1-R/ES/	en
dc.relation.publisherversion	https://doi.org/10.1038/s41598-018-25232-y
dc.rights	© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.	en
dc.rights.accessRights	info:eu-repo/semantics/openAccess
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject	Bacterial pathogenesis	en
dc.subject	Infection	en
dc.title	Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways	en
dc.type	info:eu-repo/semantics/article
dc.type.version	info:eu-repo/semantics/publishedVersion	en
dc.type.version	Versión publicada / Argitaratu den bertsioa	es
dspace.entity.type	Publication
relation.isAuthorOfPublication	eab5adde-437b-46f6-9496-2fa2b16b308f
relation.isAuthorOfPublication	94ad1041-7e91-4171-9452-f4e270bd5dee
relation.isAuthorOfPublication	bcd76277-79d9-4cf7-b6bd-f172dabe984b
relation.isAuthorOfPublication	0e8e1c09-428a-47b7-819c-7c372f0c7242
relation.isAuthorOfPublication.latestForDiscovery	eab5adde-437b-46f6-9496-2fa2b16b308f