Show simple item record

Article

dc.creatorMiró-Canturri, Andreaes
dc.creatorAyerbe Algaba, Rafaeles
dc.creatorVila-Domínguez, Andreaes
dc.creatorJiménez-Mejías, Manuel Enriquees
dc.creatorPachón Díaz, Jerónimoes
dc.date.accessioned2021-05-04T08:21:43Z
dc.date.available2021-05-04T08:21:43Z
dc.date.issued2021-03-22
dc.identifier.citationMiró-Canturri, A., Ayerbe Algaba, R., Vila-Domínguez, A., Jiménez-Mejías, M.E. y Pachón, J. (2021). Repurposing of the tamoxifen metabolites to combat infections by multidrug-resistant gram-negative bacilli. Antibiotics, 10 (3), 1-8.
dc.identifier.issn2079-6382es
dc.identifier.urihttps://hdl.handle.net/11441/108395
dc.description.abstractThe development of new strategic antimicrobial therapeutic approaches, such as drug repurposing, has become an urgent need. Previously, we reported that tamoxifen presents therapeutic efficacy against multidrug-resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli in experimental infection models by modulating innate immune system cell traffic. The main objective of this study was to analyze the activity of N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen, three major metabolites of tamoxifen, against these pathogens. We showed that immunosuppressed mice infected with A. baumannii, P. aeruginosa, or E. coli in peritoneal sepsis models and treated with tamoxifen at 80 mg/kg/d for three days still reduced the bacterial load in tissues and blood. Moreover, it increased mice survival to 66.7% (for A. baumannii and E. coli) and 16.7% (for P. aeruginosa) when compared with immunocompetent mice. Further, susceptibility and time-kill assays showed that N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen exhibited minimum inhibitory concentration of the 90% of the isolates (MIC90) values of 16 mg/L, and were bactericidal against clinical isolates of A. baumannii and E. coli. This antimicrobial activity of tamoxifen metabolites paralleled an increased membrane permeability of A. baumannii and E. coli without affecting their outer membrane proteins profiles. Together, these data showed that tamoxifen metabolites presented antibacterial activity against MDR A. baumannii and E. coli, and may be a potential alternative for the treatment of infections caused by these two pathogens.es
dc.description.sponsorshipInstituto de Salud Carlos III, Proyectos de Investigación en Salud (becas PI16 / 01378 y PI19 / 01453)es
dc.description.sponsorshipPlan Nacional de I + D + i 2013-2016 y el Instituto de Salud Carlos IIIes
dc.description.sponsorshipRed Española de Investigación en Enfermedades Infecciosas (REIPI RD16 / 0016/0009)es
dc.description.sponsorshipounes Smani cuenta con el apoyo del Subprograma Miguel Servet Tipo I del Ministerio de Economía y Competitividad de España (CP15 / 00132).es
dc.formatapplication/pdfes
dc.format.extent8es
dc.language.isoenges
dc.publisherMultidisciplinary Digital Publishing Institutees
dc.relation.ispartofAntibiotics, 10 (3), 1-8.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectTamoxifenes
dc.subjectTamoxifen metabolitees
dc.subjectBacteriaes
dc.subjectInfectiones
dc.subjectTreatmentes
dc.titleRepurposing of the tamoxifen metabolites to combat infections by multidrug-resistant gram-negative bacillies
dc.typeinfo:eu-repo/semantics/articlees
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessrightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Medicinaes
dc.relation.projectIDPI16 / 01378es
dc.relation.projectIDPI19 / 01453)es
dc.relation.projectIDREIPI RD16 / 0016/0009es
dc.relation.projectIDCP15 / 00132es
dc.relation.publisherversionhttps://doi.org/10.3390/antibiotics10030336es
dc.identifier.doi10.3390/antibiotics10030336es
dc.contributor.groupInstituto de Biomedicina de Sevilla (IBIS). Grupo de Investigación: CTS-203 Estudio de las Enfermedades Infecciosases
dc.journaltitleAntibioticses
dc.publication.volumen10es
dc.publication.issue3es
dc.publication.initialPage1es
dc.publication.endPage8es

FilesSizeFormatViewDescription
Repurposing of the tamoxifen ...1.265MbIcon   [PDF] View/Open  

This item appears in the following collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Except where otherwise noted, this item's license is described as: Attribution-NonCommercial-NoDerivatives 4.0 Internacional