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dc.contributor.authorMartín Plágaro, César Augusto
dc.contributor.authorEtxaniz Iriondo, Asier
dc.contributor.authorBelloso Uribe, Kepa
dc.contributor.authorEtxebarria Gallego, Aitor
dc.contributor.authorGonzález Bullón, David ORCID
dc.contributor.authorArluzea de Jauregizar, Jon Andoni ORCID
dc.contributor.authorGoñi Urcelay, Félix María ORCID
dc.contributor.authorArechaga Martínez, Juan Miguel ORCID
dc.contributor.authorOstolaza Echabe, Elena Amaya
dc.date.accessioned2016-04-06T14:17:33Z
dc.date.available2016-04-06T14:17:33Z
dc.date.issued2015-09-08
dc.identifier.citationScientific Reports 5 : (2015) // Article ID 13774es
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10810/17820
dc.description.abstractBordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. Though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. However the precise mechanism used by B. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. Here we find that adenylate cyclase toxin (ACT), one of the important toxins of B. pertussis, is sufficient to promote bacterial internalisation into non-phagocytic cells. After characterization of the entry route we show that uptake of "toxin-coated bacteria" proceeds via a clathrin-independent, caveolae-dependent entry pathway, allowing the internalised bacteria to survive within the cells. Intracellular bacteria were found inside non-acidic endosomes with high sphingomyelin and cholesterol content, or "free" in the cytosol of the invaded cells, suggesting that the ACT-induced bacterial uptake may not proceed through formation of late endolysosomes. Activation of Tyr kinases and toxin-induced Ca2+-influx are essential for the entry process. We hypothesize that B. pertussis might use ACT to activate the endocytic machinery of non-phagocytic cells and gain entry into these cells, in this way evading the host immune system.es
dc.description.sponsorshipTechnical and human support provided by SGIker (Analytical and High-Resolution Microscopy in Biomedicine Service of UPV/EHU) and Rocio Alonso for excellent technical assistance are gratefully acknowledged. We also thank Dr. N. Guiso from the Pasteur Institute (Paris, France) for the Bordetella pertussis strains BP18323 and non-virulent bgv negative BP18323H-. This study was supported by grants from the Spanish Ministerio de Ciencia y Tecnologia (Project BFU 2012-36241), and the Basque Government (Grupos Consolidados IT849-13 and ETORTEK Program). K.B.U and D.G.B. were recipients of a fellowship from the Bizkaia Biophysics Foundation. A.E.G. was a recipient of a research contract (INNPACTO 2010) and A.E.L. was a recipient of a fellowship from the University of the Basque Country (UPV/EH). A patent with reference N/Ref.: P1683USPC (2004) was approved.es
dc.language.isoenges
dc.publisherNature Publishing Groupes
dc.relationinfo:eu-repo/grantAgreement/MINECO/BFU2012-36241
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectrespiratory epithelial-cellses
dc.subjectgly-asp sequencees
dc.subjectbordetella-pertussises
dc.subjectfilamentous hemagglutinines
dc.subjectintracellular survivales
dc.subjectvirulence factorses
dc.subjecthuman macrophageses
dc.subjectmammalian-cellses
dc.subjecttarget-cellses
dc.subjectinvasiones
dc.titleAdenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cellses
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holderThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/es
dc.relation.publisherversionhttp://www.nature.com/articles/srep13774#abstractes
dc.identifier.doi10.1038/srep13774
dc.departamentoesBiología celular e histologíaes_ES
dc.departamentoesBioquímica y biología moleculares_ES
dc.departamentoeuZelulen biologia eta histologiaes_ES
dc.departamentoeuBiokimika eta biologia molekularraes_ES
dc.subject.categoriaMULTIDISCIPLINARY SCIENCES


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