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dc.creatorConde Álvarez, Raqueles_ES
dc.creatorPalacios Chaves, Leyrees_ES
dc.creatorGil Ramírez, Yolandaes_ES
dc.creatorSalvador Bescós, Miriames_ES
dc.creatorBárcena Varela, Marinaes_ES
dc.creatorAragón Aranda, Beatrizes_ES
dc.creatorMartínez Gómez, Estrellaes_ES
dc.creatorZúñiga Ripa, Amaiaes_ES
dc.creatorMiguel López, María Jesús dees_ES
dc.creatorBartholomew, Toby Leighes_ES
dc.creatorHanniffy, Seanes_ES
dc.creatorGrilló Dolset, María Jesúses_ES
dc.creatorVences Guzmán, Miguel Ángeles_ES
dc.creatorBengoechea Alonso, José Antonioes_ES
dc.creatorArce Gorvel, Vilmaes_ES
dc.creatorGorvel, Jean-Pierrees_ES
dc.creatorMoriyón Uría, Ignacioes_ES
dc.creatorIriarte, Maitees_ES
dc.date.accessioned2018-09-04T06:43:47Z
dc.date.available2018-09-04T06:43:47Z
dc.date.issued2018
dc.identifier.issn1664-302X (Electronic)
dc.identifier.urihttps://hdl.handle.net/2454/30432
dc.description.abstractThe brucellae are facultative intracellular bacteria that cause a worldwide extended zoonosis. One of the pathogenicity mechanisms of these bacteria is their ability to avoid rapid recognition by innate immunity because of a reduction of the pathogen-associated molecular pattern (PAMP) of the lipopolysaccharide (LPS), free-lipids, and other envelope molecules. We investigated the Brucella homologs of lptA, lpxE, and lpxO, three genes that in some pathogens encode enzymes that mask the LPS PAMP by upsetting the core-lipid A charge/hydrophobic balance. Brucella lptA, which encodes a putative ethanolamine transferase, carries a frame-shift in B. abortus but not in other Brucella spp. and phylogenetic neighbors like the opportunistic pathogen Ochrobactrum anthropi. Consistent with the genomic evidence, a B. melitensis lptA mutant lacked lipid A-linked ethanolamine and displayed increased sensitivity to polymyxin B (a surrogate of innate immunity bactericidal peptides), while B. abortus carrying B. melitensis lptA displayed increased resistance. Brucella lpxE encodes a putative phosphatase acting on lipid A or on a free-lipid that is highly conserved in all brucellae and O. anthropi. Although we found no evidence of lipid A dephosphorylation, a B. abortus lpxE mutant showed increased polymyxin B sensitivity, suggesting the existence of a hitherto unidentified free-lipid involved in bactericidal peptide resistance. Gene lpxO putatively encoding an acyl hydroxylase carries a frame-shift in all brucellae except B. microti and is intact in O. anthropi. Free-lipid analysis revealed that lpxO corresponded to olsC, the gene coding for the ornithine lipid (OL) acyl hydroxylase active in O. anthropi and B. microti, while B. abortus carrying the olsC of O. anthropi and B. microti synthesized hydroxylated OLs. Interestingly, mutants in lptA, lpxE, or olsC were not attenuated in dendritic cells or mice. This lack of an obvious effect on virulence together with the presence of the intact homolog genes in O. anthropi and B. microti but not in other brucellae suggests that LptA, LpxE, or OL β-hydroxylase do not significantly alter the PAMP properties of Brucella LPS and free-lipids and are therefore not positively selected during the adaptation to intracellular life.en
dc.description.sponsorshipThis research was supported by the Institute for Tropical Health funders (Obra Social la CAIXA, Fundaciones Caja Navarra and Roviralta, PROFAND, Ubesol, ACUNSA, and Artai) and grants MINECO (AGL2014-58795-C4-1-R, Bru-Epidia 291815-FP7/ERANET/ANIHWA), Aragón Government (Consolidated Group A14), and Marie Curie Career Integration Grant U-KARE (PCIG13-GA-2013-618162). TLB is the recipient of a Ph.D. Fellowship funded by the Department for Employment and Learning (Northern Ireland, United Kingdom).en
dc.format.extent14 p.
dc.format.mimetypeapplication/pdfen
dc.format.mimetypeapplication/zipen
dc.language.isoengen
dc.publisherFrontiers Mediaen
dc.relation.ispartofFrontiers in Microbiology, 8: 2657en
dc.rights© 2018 Conde-Álvarez, Palacios-Chaves, Gil-Ramírez, Salvador-Bescós, Bárcena-Varela, Aragón-Aranda, Martínez-Gómez, Zúñiga-Ripa, de Miguel, Bartholomew, Hanniffy, Grilló, Vences-Guzmán, Bengoechea, Arce-Gorvel, Gorvel, Moriyón and Iriarte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectLipopolysaccharideen
dc.subjectBrucellaen
dc.subjectLipidsen
dc.subjectCell envelopeen
dc.subjectPAMPen
dc.titleIdentification of lptA, lpxE, and lpxO, three genes involved in the remodeling of Brucella cell envelopeen
dc.typeinfo:eu-repo/semantics/articleen
dc.typeArtículo / Artikuluaes
dc.contributor.departmentIdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutuaes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.identifier.doi10.3389/fmicb.2017.02657
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//AGL2014-58795-C4-1-R/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/European Commission/FP7/291815en
dc.relation.projectIDinfo:eu-repo/grantAgreement/European Commission/FP7/618162en
dc.relation.publisherversionhttps://doi.org/10.3389/fmicb.2017.02657
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.type.versionVersión publicada / Argitaratu den bertsioaes


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© 2018 Conde-Álvarez, Palacios-Chaves, Gil-Ramírez, Salvador-Bescós, Bárcena-Varela, Aragón-Aranda, Martínez-Gómez, Zúñiga-Ripa, de Miguel, Bartholomew, Hanniffy, Grilló, Vences-Guzmán, Bengoechea, Arce-Gorvel, Gorvel, Moriyón and Iriarte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Except where otherwise noted, this item's license is described as © 2018 Conde-Álvarez, Palacios-Chaves, Gil-Ramírez, Salvador-Bescós, Bárcena-Varela, Aragón-Aranda, Martínez-Gómez, Zúñiga-Ripa, de Miguel, Bartholomew, Hanniffy, Grilló, Vences-Guzmán, Bengoechea, Arce-Gorvel, Gorvel, Moriyón and Iriarte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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