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dc.contributor.authorVinuesa, Víctor
dc.contributor.authorCruces Fernández, Raquel 
dc.contributor.authorNonnoi, Francesca
dc.contributor.authorMcConnell, Michael J
dc.identifier.citationAntibiotics (Basel). 2021 May 20;10(5):609.es_ES
dc.description.abstractInfections caused by multidrug-resistant Acinetobacter baumannii would benefit from the development of novel treatment approaches. Compounds that interfere with bacterial iron metabolism, such as iron chelators and gallium nitrate, have previously been shown to have antimicrobial activity against A. baumannii. In this study, we characterize the effect of LpxC inhibitors on the antimicrobial activity of previously characterized iron chelators, 2,2'-bipyridyl (BIP) and deferiprone (DFP), and gallium nitrate (Ga(NO3)3) against A. baumannii reference strains and multidrug-resistant clinical isolates. The LpxC inhibitor LpxC-2 was synergistic with BIP for 30% of strains tested (FICI values: 0.38-1.02), whereas inhibition with LpxC-4 was synergistic with BIP for 60% of strains tested (FICI values: 0.09-0.75). In time-kill assays, combinations of BIP with both LpxC inhibitors demonstrated synergistic activity, with a more than 3 log10 reduction in bacterial counts compared to BIP alone. LpxC-2 was synergistic with Ga(NO3)3 for 50% of strains tested (FICI values: 0.27-1.0), whereas LpxC-4 was synergistic with Ga(NO3)3 for all strains tested (FICI values: 0.08-≤0.50). In time-kill assays, combinations of Ga(NO3)3 with LpxC-2 and LpxC-4 decreased the growth of both strains compared to each compound separately; however, only the combination with LpxC-4 met the defined criteria for synergy. These results identify a novel synergy between two antimicrobial classes against A. baumannii strains.es_ES
dc.description.sponsorshipThis research was supported by grants MPY 380/18 from the Instituto de Salud Carlos III (ISCIII) awarded to M.J.M. V.V. is supported by the Río Hortega Program from the Instituto de Salud Carlos III. The APC was funded by MPY 380/18 from the Instituto de Salud Carlos III (ISCIII) awarded to M.J.M.es_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.subjectLpxC inhibitorses_ES
dc.subjectIron chelatorses_ES
dc.subjectAntibiotic resistancees_ES
dc.titleInhibition of LpxC Increases the Activity of Iron Chelators and Gallium Nitrate in Multidrug-Resistant Acinetobacter baumanniies_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.identifier.journalAntibiotics (Basel, Switzerland)es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/MPY 380/18es_ES
dc.rights.accessRightsopen accesses_ES

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