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dc.creatorFerrer-Espada, R. (Raquel)-
dc.creatorShahrour, H. (Hawraa)-
dc.creatorPitts, B. (Betsey)-
dc.creatorStewart, P.S. (Philip S.)-
dc.creatorSánchez-Gómez, S. (Susana)-
dc.creatorMartinez-de-Tejada, G. (Guillermo)-
dc.date.accessioned2021-10-04T10:47:10Z-
dc.date.available2021-10-04T10:47:10Z-
dc.date.issued2019-
dc.identifier.citationFerrer-Espada, R. (Raquel); Shahrour, H. (Hawraa); Pitts, B. (Betsey); et al. "A permeability-increasing drug synergizes with bacterial efux pump inhibitors and restores susceptibility to antibiotics in multi-drug resistant Pseudomonas aeruginosa strains". Scientific Reports. 9 (3452), 2019, 1 - 12es
dc.identifier.issn2045-2322-
dc.identifier.otherPMID: 30837499-
dc.identifier.urihttps://hdl.handle.net/10171/62141-
dc.description.abstractResistance to antibiotics poses a major global threat according to the World Health Organization. Restoring the activity of existing drugs is an attractive alternative to address this challenge. One of the most efficient mechanisms of bacterial resistance involves the expression of efflux pump systems capable of expelling antibiotics from the cell. Although there are efflux pump inhibitors (EPIs) available, these molecules are toxic for humans. We hypothesized that permeability-increasing antimicrobial peptides (AMPs) could lower the amount of EPI necessary to sensitize bacteria to antibiotics that are efflux substrates. To test this hypothesis, we measured the ability of polymyxin B nonapeptide (PMBN), to synergize with antibiotics in the presence of EPIs. Assays were performed using planktonic and biofilm-forming cells of Pseudomonas aeruginosa strains overexpressing the MexAB-OprM efflux system. Synergy between PMBN and EPIs boosted azithromycin activity by a factor of 2,133 and sensitized P. aeruginosa to all tested antibiotics. This reduced several orders of magnitude the amount of inhibitor needed for antibiotic sensitization. The selected antibiotic-EPI-PMBN combination caused a 10 million-fold reduction in the viability of biofilm forming cells. We proved that AMPs can synergize with EPIs and that this phenomenon can be exploited to sensitize bacteria to antibiotics.es_ES
dc.description.sponsorshipTis work was supported by the Proyectos de Investigación Universidad de Navarra, Spain (PIUNA-P2011-17 and P2015-14 to G. M. T.) and a doctoral fellowship from Gobierno Vasco, Spain (BFI-2011-9 to R. F. E).es_ES
dc.language.isoenges_ES
dc.publisherSpringer Science and Business Media LLCes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectMaterias Investigacion::Ciencias de la Salud::Microbiología y biología moleculares_ES
dc.titleA permeability-increasing drug synergizes with bacterial efux pump inhibitors and restores susceptibility to antibiotics in multi-drug resistant Pseudomonas aeruginosa strainses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.description.noteThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madees_ES
dc.identifier.doi10.1038/s41598-019-39659-4-
dadun.citation.endingPage12es_ES
dadun.citation.number3452es_ES
dadun.citation.publicationNameScientific Reportses_ES
dadun.citation.startingPage1es_ES
dadun.citation.volume9es_ES

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