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dc.creatorSánchez-Gómez, S. (Susana)-
dc.creatorJapelj, B. (Bostjan)-
dc.creatorJerala, R. (Roman)-
dc.creatorMoriyon, I. (Ignacio)-
dc.creatorFernández-Alonso, M. (Miriam)-
dc.creatorLeiva, J. (José)-
dc.creatorBlondelle, S.E. (Sylvie E.)-
dc.creatorAndrä, J. (Jörg)-
dc.creatorBrandenburg, K. (Klaus)-
dc.creatorLohner, K. (Karl)-
dc.creatorMartinez-de-Tejada, G. (Guillermo)-
dc.date.accessioned2013-08-30T11:57:29Z-
dc.date.available2013-08-30T11:57:29Z-
dc.date.issued2011-
dc.identifier.citationSanchez-Gomez S, Japelj B, Jerala R, Moriyon I, Fernandez Alonso M, Leiva J, et al. Structural features governing the activity of lactoferricin-derived peptides that act in synergy with antibiotics against Pseudomonas aeruginosa in vitro and in vivo. Antimicrob Agents Chemother 2011 Jan;55(1):218-228.es_ES
dc.identifier.issn1098-6596-
dc.identifier.urihttps://hdl.handle.net/10171/29639-
dc.description.abstractPseudomonas aeruginosa is naturally resistant to many antibiotics, and infections caused by this organism are a serious threat, especially to hospitalized patients. The intrinsic low permeability of P. aeruginosa to antibiotics results from the coordinated action of several mechanisms, such as the presence of restrictive porins and the expression of multidrug efflux pump systems. Our goal was to develop antimicrobial peptides with an improved bacterial membrane-permeabilizing ability, so that they enhance the antibacterial activity of antibiotics. We carried out a structure activity relationship analysis to investigate the parameters that govern the permeabilizing activity of short (8- to 12-amino-acid) lactoferricin-derived peptides. We used a new class of constitutional and sequence-dependent descriptors called PEDES (peptide descriptors from sequence) that allowed us to predict (Spearman's ρ = 0.74; P < 0.001) the permeabilizing activity of a new peptide generation. To study if peptide-mediated permeabilization could neutralize antibiotic resistance mechanisms, the most potent peptides were combined with antibiotics, and the antimicrobial activities of the combinations were determined on P. aeruginosa strains whose mechanisms of resistance to those antibiotics had been previously characterized. A subinhibitory concentration of compound P2-15 or P2-27 sensitized P. aeruginosa to most classes of antibiotics tested and counteracted several mechanisms of antibiotic resistance, including loss of the OprD porin and overexpression of several multidrug efflux pump systems. Using a mouse model of lethal infection, we demonstrated that whereas P2-15 and erythromycin were unable to protect mice when administered separately, concomitant administration of the compounds afforded long-lasting protection to one-third of the animals.es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Microbiologyes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectAnti-Bacterial Agents pharmacologyes_ES
dc.subjectAnti-Bacterial Agents therapeutic usees_ES
dc.subjectLactoferrin chemistryes_ES
dc.subjectPeptides pharmacologyes_ES
dc.subjectPeptides therapeutic usees_ES
dc.subjectPseudomonas Infections drug therapyes_ES
dc.subjectPseudomonas aeruginosa drug effectses_ES
dc.subjectFemalees_ES
dc.titleStructural features governing the activity of lactoferricin-derived peptides that act in synergy with antibiotics against Pseudomonas aeruginosa in vitro and in vivoes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.type.driverinfo:eu-repo/semantics/articlees_ES

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