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dc.contributor.authorPhelan, James
dc.date.accessioned2021-09-14T17:24:39Z
dc.date.available2021-09-14T17:24:39Z
dc.date.issued2021
dc.date.submitted2021en
dc.identifier.citationCahill C, O'Connell F, Gogan KM, Cox DJ, Basdeo SA, O'Sullivan J, Gordon SV, Keane J, Phelan JJ. The Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCG, International Journal of Molecular Sciences, 2021 Mar 13;22(6):2938en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/97069
dc.descriptionPUBLISHEDen
dc.description.abstractFor over 50 years, patients with drug-sensitive and drug-resistant tuberculosis have undergone long, arduous, and complex treatment processes with several antimicrobials. With the prevalence of drug-resistant strains on the rise and new therapies for tuberculosis urgently required, we assessed whether manipulating iron levels in macrophages infected with mycobacteria offered some insight into improving current antimicrobials that are used to treat drug-resistant tuberculosis. We investigated if the iron chelator, desferrioxamine, can support the function of human macrophages treated with an array of second-line antimicrobials, including moxifloxacin, bedaquiline, amikacin, clofazimine, linezolid and cycloserine. Primary human monocyte-derived macrophages were infected with Bacillus Calmette-Guérin (BCG), which is pyrazinamide-resistant, and concomitantly treated for 5 days with desferrioxamine in combination with each one of the second-line tuberculosis antimicrobials. Our data indicate that desferrioxamine used as an adjunctive treatment to bedaquiline significantly reduced the bacterial load in human macrophages infected with BCG. Our findings also reveal a link between enhanced bactericidal activity and increases in specific cytokines, as the addition of desferrioxamine increased levels of IFN-γ, IL-6, and IL-1β in BCG-infected human monocyte-derived macrophages (hMDMs) treated with bedaquiline. These results provide insight, and an in vitro proof-of-concept, that iron chelators may prove an effective adjunctive therapy in combination with current tuberculosis antimicrobials. Keywords:en
dc.language.isoenen
dc.relation.ispartofseriesInternational Journal of Molecular Sciences;
dc.rightsYen
dc.subjectBCGen
dc.subjectTuberculosisen
dc.subjectIron metabolismen
dc.subjectIron chelationen
dc.subjectAntimicrobialsen
dc.subjectDrug-resistant tuberculosisen
dc.subjectHost-directed therapyen
dc.subjectInterferon-γen
dc.titleThe Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCGen
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/phelanj3
dc.identifier.rssinternalid233149
dc.identifier.doi10.3390/ijms22062938
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumber18/TIDA/6026en
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.identifier.rssurihttps://pubmed.ncbi.nlm.nih.gov/33805837/
dc.identifier.orcid_id0000-0001-9431-2002
dc.status.accessibleNen


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