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Deciphering tissue-induced Klebsiella pneumoniae lipid A structure
dc.creator | Llobet, Enrique | es_ES |
dc.creator | Martínez Moliner, Verónica | es_ES |
dc.creator | Moranta, David | es_ES |
dc.creator | Dahlström, Käthe M. | es_ES |
dc.creator | Regueiro, Verónica | es_ES |
dc.creator | Tomás, Anna | es_ES |
dc.creator | Cano, Victoria | es_ES |
dc.creator | Pérez Gutiérrez, Camino | es_ES |
dc.creator | Frank, Christian G. | es_ES |
dc.creator | Garmendia García, Juncal | es_ES |
dc.date.accessioned | 2018-12-28T09:14:07Z | |
dc.date.available | 2018-12-28T09:14:07Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 0027-8424 (Print) | |
dc.identifier.issn | 1091-6490 (Electronic) | |
dc.identifier.uri | https://hdl.handle.net/2454/31891 | |
dc.description.abstract | The outcome of an infection depends on host recognition of the pathogen, hence leading to the activation of signaling pathways controlling defense responses. A long-held belief is that the modification of the lipid A moiety of the lipopolysaccharide could help Gram-negative pathogens to evade innate immunity. However, direct evidence that this happens in vivo is lacking. Here we report the lipid A expressed in the tissues of infected mice by the human pathogen Klebsiella pneumoniae. Our findings demonstrate that Klebsiella remodels its lipid A in a tissue-dependent manner. Lipid A species found in the lungs are consistent with a 2-hydroxyacylmodified lipid A dependent on the PhoPQ-regulated oxygenase LpxO. The in vivo lipid A pattern is lost in minimally passaged bacteria isolated from the tissues. LpxO-dependent modification reduces the activation of inflammatory responses and mediates resistance to antimicrobial peptides. An lpxO mutant is attenuated in vivo thereby highlighting the importance of this lipid A modification in Klebsiella infection biology. Colistin, one of the last options to treat multidrugresistant Klebsiella infections, triggers the in vivo lipid A pattern. Moreover, colistin-resistant isolates already express the in vivo lipid A pattern. In these isolates, LpxO-dependent lipid A modification mediates resistance to colistin. Deciphering the lipid A expressed in vivo opens the possibility of designing novel therapeutics targeting the enzymes responsible for the in vivo lipid A pattern. | en |
dc.description.sponsorship | This work was also supported by a Spanish Ministry of Economy and Competitiveness Grant (Biomedicine Programme, SAF2012-39841), Marie Curie Career Integration Grant U-KARE (PCIG13-GA-2013-618162), and Queen’s University Belfast start-up funds (to J.A.B.). | en |
dc.format.extent | 10 p. | |
dc.format.mimetype | application/pdf | en |
dc.format.mimetype | application/zip | en |
dc.language.iso | eng | en |
dc.publisher | National Academy of Sciences | en |
dc.relation.ispartof | PNAS November 17, 2015 112 (46) E6369-E6378 | en |
dc.subject | Lipid A | en |
dc.subject | Klebsiella | en |
dc.subject | Colistin | en |
dc.subject | LpxO | en |
dc.subject | PhoPQ | en |
dc.title | Deciphering tissue-induced Klebsiella pneumoniae lipid A structure | en |
dc.type | info:eu-repo/semantics/article | en |
dc.type | Artículo / Artikulua | es |
dc.contributor.department | IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | en |
dc.rights.accessRights | Acceso abierto / Sarbide irekia | es |
dc.identifier.doi | 10.1073/pnas.1508820112 | |
dc.relation.projectID | info:eu-repo/grantAgreement/MINECO//SAF2012-39841/ES/ | en |
dc.relation.publisherversion | https://doi.org/10.1073/pnas.1508820112 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.type.version | Versión publicada / Argitaratu den bertsioa | es |