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dc.contributor.author | Torrens, Gabriel | |
dc.contributor.author | Pérez-Gallego, Marcelo | |
dc.contributor.author | Moya, Bartolome | |
dc.contributor.author | Munar-Bestard, Marta | |
dc.contributor.author | Zamorano, Laura | |
dc.contributor.author | Cabot, Gabriel | |
dc.contributor.author | Blazquez, Jesus | |
dc.contributor.author | Ayala, Juan A | |
dc.contributor.author | Oliver, Antonio | |
dc.contributor.author | Juan, Carlos | |
dc.date.accessioned | 2024-07-11T09:10:38Z | |
dc.date.available | 2024-07-11T09:10:38Z | |
dc.date.issued | 2017-07-25 | |
dc.identifier.citation | Torrens Ribot G, Perez-Gallego M, Moya Cañellas B, Munar Bestard M, Zamorano Paez L, Cabot G, et al. Targeting the permeability barrier and peptidoglycan recycling pathways to disarm Pseudomonas aeruginosa against the innate immune system. PLoS One. 2017 Jul 25;12(7):e0181932. | en |
dc.identifier.issn | 1932-6203 | |
dc.identifier.other | http://hdl.handle.net/20.500.13003/9741 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20444 | |
dc.description.abstract | Antimicrobial resistance is a continuously increasing threat that severely compromises our antibiotic arsenal and causes thousands of deaths due to hospital-acquired infections by pathogens such as Pseudomonas aeruginosa, situation further aggravated by the limited development of new antibiotics. Thus, alternative strategies such as those targeting bacterial resistance mechanisms, virulence or potentiating the activity of our immune system resources are urgently needed. We have recently shown that mutations simultaneously causing the peptidoglycan recycling blockage and the beta-lactamase AmpC overexpression impair the virulence of P. aeruginosa. These findings suggested that peptidoglycan metabolism might be a good target not only for fighting antibiotic resistance, but also for the attenuation of virulence and/ or potentiation of our innate immune weapons. Here we analyzed the activity of the innate immune elements peptidoglycan recognition proteins (PGRPs) and lysozyme against P. aeruginosa. We show that while lysozyme and PGRPs have a very modest basal effect over P. aeruginosa, their bactericidal activity is dramatically increased in the presence of subinhibitory concentrations of the permeabilizing agent colistin. We also show that the P. aeruginosa lysozyme inhibitors seem to play a very residual protective role even in permeabilizing conditions. In contrast, we demonstrate that, once the permeability barrier is overpassed, the activity of lysozyme and PGRPs is dramatically enhanced when inhibiting key peptidoglycan recycling components (such as the 3 AmpDs, AmpG or NagZ), indicating a decisive protective role for cell-wall recycling and that direct peptidoglycan-binding supports, at least partially, the activity of these enzymes. Finally, we show that recycling blockade when occurring simultaneously with AmpC overexpression determines a further decrease in the resistance against PGRP2 and lysozyme, linked to quantitative changes in the cell-wall. Thus, our results help to delineate new strategies against P. aeruginosa | en |
dc.description.sponsorship | This work was supported by the Ministerio de Economia y Competitividad of Spain and Instituto de Salud CarlosIII-co-financed by European Regional Development Fund Away to achieve Europe ERDF,through the Spanish Network for the Research in Infectious Diseases (RD12/0015) and grants CP12/03324,SAF201238539, PI12/00103, PI15/00088 and PI15/02212. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. | es_ES |
dc.language.iso | eng | en |
dc.publisher | Public Library of Science (PLOS) | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Muramidase | * |
dc.subject.mesh | Peptidoglycan | * |
dc.subject.mesh | Colistin | * |
dc.subject.mesh | Anti-Bacterial Agents | * |
dc.subject.mesh | Nod Signaling Adaptor Proteins | * |
dc.subject.mesh | Microbial Sensitivity Tests | * |
dc.subject.mesh | Gene Knockdown Techniques | * |
dc.subject.mesh | Pseudomonas aeruginosa | * |
dc.subject.mesh | Carrier Proteins | * |
dc.subject.mesh | Immunity, Innate | * |
dc.subject.mesh | Cell Membrane Permeability | * |
dc.title | Targeting the permeability barrier and peptidoglycan recycling pathways to disarm Pseudomonas aeruginosa against the innate immune system | en |
dc.type | research article | en |
dc.rights.license | Attribution 4.0 International | * |
dc.identifier.pubmedID | 28742861 | es_ES |
dc.format.volume | 12 | es_ES |
dc.format.number | 7 | es_ES |
dc.format.page | e0181932 | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0181932 | |
dc.relation.publisherversion | https://dx.doi.org/10.1371/journal.pone.0181932 | en |
dc.identifier.journal | PloS One | es_ES |
dc.rights.accessRights | open access | en |
dc.subject.decs | Proteínas Portadoras | * |
dc.subject.decs | Permeabilidad de la Membrana Celular | * |
dc.subject.decs | Pruebas de Sensibilidad Microbiana | * |
dc.subject.decs | Peptidoglicano | * |
dc.subject.decs | Muramidasa | * |
dc.subject.decs | Colistina | * |
dc.subject.decs | Inmunidad Innata | * |
dc.subject.decs | Proteínas Adaptadoras de Señalización NOD | * |
dc.subject.decs | Pseudomonas aeruginosa | * |
dc.subject.decs | Antibacterianos | * |
dc.subject.decs | Técnicas de Silenciamiento del Gen | * |
dc.identifier.scopus | 2-s2.0-85025825486 | |
dc.identifier.wos | 406370000062 | |
dc.identifier.pui | L617479954 |
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