{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:01:25Z","timestamp":1790755285395,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"crossref","award":["K2012-3469"],"award-info":[{"award-number":["K2012-3469"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"crossref","award":["K2013-8621"],"award-info":[{"award-number":["K2013-8621"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The reasons why aminoglycosides are bactericidal have not been not fully elucidated, and evidence indicates that the cidal effects are at least partly dependent on iron. We demonstrate that availability of iron markedly affects the susceptibility of the facultative intracellular bacterium<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Francisella tularensis<\/jats:named-content>strain SCHU S4 to the aminoglycoside gentamicin. Specifically, the intracellular depots of iron were inversely correlated to gentamicin susceptibility, whereas the extracellular iron concentrations were directly correlated to the susceptibility. Further proof of the intimate link between iron availability and antibiotic susceptibility were the findings that a \u0394<jats:italic>fslA<\/jats:italic>mutant, which is defective for siderophore-dependent uptake of ferric iron, showed enhanced gentamicin susceptibility and that a \u0394<jats:italic>feoB<\/jats:italic>mutant, which is defective for uptake of ferrous iron, displayed complete growth arrest in the presence of gentamicin. Based on the aforementioned findings, it was hypothesized that gallium could potentiate the effect of gentamicin, since gallium is sequestered by iron uptake systems. The ferrozine assay demonstrated that the presence of gallium inhibited &gt;70% of the iron uptake. Addition of gentamicin and\/or gallium to infected bone marrow-derived macrophages showed that both 100 \u03bcM gallium and 10 \u03bcg\/ml of gentamicin inhibited intracellular growth of SCHU S4 and that the combined treatment acted synergistically. Moreover, treatment of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">F. tularensis<\/jats:named-content>-infected mice with gentamicin and gallium showed an additive effect. Collectively, the data demonstrate that SCHU S4 is dependent on iron to minimize the effects of gentamicin and that gallium, by inhibiting the iron uptake, potentiates the bactericidal effect of gentamicin<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/aac.01240-15","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T02:34:05Z","timestamp":1445913245000},"page":"288-295","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Gallium Potentiates the Antibacterial Effect of Gentamicin against Francisella tularensis"],"prefix":"10.1128","volume":"60","author":[{"given":"Helena","family":"Lindgren","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology, Clinical Bacteriology, and Laboratory for Molecular Infection Medicine Sweden, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Sj\u00f6stedt","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Clinical Bacteriology, and Laboratory for Molecular Infection Medicine Sweden, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00088903"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1409.009"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1409.014"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093558"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.371856"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.072835-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1409.017"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01584-07"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.4.727"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006055"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.049"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232751"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1238328"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1219192"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.127456"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02013900"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1699-0463.1994.tb04868.x","article-title":"The antibacterial activity of a siderophore. 3. 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Preclinical toxicology and tissue gallium distribution of a novel antitumour gallium compound: tris (8-quinolinolato) gallium (III). 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