{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:07:03Z","timestamp":1791317223281,"version":"4.3.1"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2010,10,1]],"date-time":"2010-10-01T00:00:00Z","timestamp":1285891200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The Gram-negative pathogen<jats:italic>Francisella tularensis<\/jats:italic>secretes a siderophore to obtain essential iron by a TonB-independent mechanism. The<jats:italic>fslABCDE<\/jats:italic>locus, encoding siderophore-related functions, is conserved among different<jats:italic>Francisella<\/jats:italic>strains. In the virulent strain Schu S4,<jats:italic>fslE<\/jats:italic>is essential for siderophore utilization and for growth under conditions of iron limitation. In contrast, we found that deletion of<jats:italic>fslE<\/jats:italic>did not affect siderophore utilization by the attenuated live vaccine strain (LVS). We found that one of the<jats:italic>fslE<\/jats:italic>paralogs encoded in the LVS genome,<jats:italic>FTL<\/jats:italic>_<jats:italic>0439<\/jats:italic>(<jats:italic>fupA\/B<\/jats:italic>), was able to partially complement a Schu S4 \u0394<jats:italic>fslE<\/jats:italic>mutant for siderophore utilization. We generated a deletion of<jats:italic>fupA\/B<\/jats:italic>in LVS and in the LVS \u0394<jats:italic>fslE<\/jats:italic>background. The \u0394<jats:italic>fupA\/B<\/jats:italic>mutant showed reduced growth under conditions of iron limitation. It was able to secrete but was unable to utilize siderophore. Mutation of both<jats:italic>fupA\/B<\/jats:italic>and<jats:italic>fslE<\/jats:italic>resulted in a growth defect of greater severity. The \u0394<jats:italic>fupA\/B<\/jats:italic>mutants showed a replication defect in J774.1A cells and decreased virulence following intraperitoneal infection in mice. Complementation of the \u0394<jats:italic>fupA\/B<\/jats:italic>mutation in<jats:italic>cis<\/jats:italic>restored the ability to utilize siderophore and concomitantly restored virulence. Our results indicate that<jats:italic>fupA\/B<\/jats:italic>plays a significant role in the siderophore-mediated iron uptake mechanism of LVS whereas<jats:italic>fslE<\/jats:italic>appears to play a secondary role. Variation in iron acquisition mechanisms may contribute to virulence differences between the strains.<\/jats:p>","DOI":"10.1128\/iai.00503-10","type":"journal-article","created":{"date-parts":[[2010,8,10]],"date-time":"2010-08-10T02:49:13Z","timestamp":1281408553000},"page":"4276-4285","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["The<i>fslE<\/i>Homolog,<i>FTL<\/i>_<i>0439<\/i>(<i>fupA\/B<\/i>), Mediates Siderophore-Dependent Iron Uptake in<i>Francisella tularensis<\/i>LVS"],"prefix":"10.1128","volume":"78","author":[{"given":"Bhaswati","family":"Sen","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Meeker","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girija","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh417"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.05.028"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01975-05"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.4049\/jimmunol.87.4.415","volume":"87","year":"1961","unstructured":"Eigelsbach, H. 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