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The [2Fe-2S] cluster-coordinating transcription factor IscR senses changes in iron and oxygen levels and plays a pivotal role in how\n                      <jats:italic toggle=\"yes\">Yersinia<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Vibrio<\/jats:italic>\n                      regulate critical virulence genes, like the type III secretion system (T3SS). We previously showed that clusterless apo-IscR promotes expression of the\n                      <jats:italic toggle=\"yes\">Yersinia pseudotuberculosis<\/jats:italic>\n                      T3SS master regulator LcrF by binding a type 2 IscR-binding motif in the\n                      <jats:italic toggle=\"yes\">lcrF<\/jats:italic>\n                      promoter, thereby facilitating T3SS expression and disseminated infection. Here, we sought to address how IscR ligation of its [2Fe-2S] cluster impacts LcrF expression and bacterial virulence. We engineered a\n                      <jats:italic toggle=\"yes\">Y. pseudotuberculosis<\/jats:italic>\n                      mutant strain with its native type 2 IscR-binding motif swapped with a type 1 motif that binds [2Fe-2S]-IscR but not apo-IscR. This\n                      <jats:italic toggle=\"yes\">lcrF<\/jats:italic>\n                      <jats:sup>pType1<\/jats:sup>\n                      mutant hyperexpressed LcrF and T3SS-associated proteins in iron-replete anaerobic conditions that favor [2Fe-2S]-IscR. To understand the consequence of this dysregulated expression, we used barcoded\n                      <jats:italic toggle=\"yes\">Y. pseudotuberculosis<\/jats:italic>\n                      libraries to probe infection dynamics of the WT and\n                      <jats:italic toggle=\"yes\">lcrF<\/jats:italic>\n                      <jats:sup>pType1<\/jats:sup>\n                      mutant strains following oral infection of mice. The\n                      <jats:italic toggle=\"yes\">lcrF<\/jats:italic>\n                      <jats:sup>pType1<\/jats:sup>\n                      mutant experienced altered colonization bottleneck and dissemination patterns compared to WT\n                      <jats:italic toggle=\"yes\">Yersinia<\/jats:italic>\n                      , suggesting that expressing LcrF and T3SS genes in response to [2Fe-2S]-IscR rather than apo-IscR may alter infection dynamics.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00358-26","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:43:37Z","timestamp":1789479817000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Switching apo- and holo-IscR control of LcrF alters how iron and oxygen regulate\n                    <i>Yersinia<\/i>\n                    virulence 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