{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:36:01Z","timestamp":1790980561154,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Bacteriol."],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Metal homeostasis in bacterial cells is a highly regulated process requiring intricately coordinated import and export, as well as precise sensing of intracellular metal concentrations. The uptake of zinc (Zn) has been linked to the virulence of<jats:named-content content-type=\"genus-species\">Brucella abortus<\/jats:named-content>; however, the capacity of<jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>strains to sense Zn levels and subsequently coordinate Zn homeostasis has not been described. Here, we show that expression of the genes encoding the zinc uptake system ZnuABC is negatively regulated by the Zn-sensing Fur family transcriptional regulator, Zur, by direct interactions between Zur and the promoter region of<jats:italic>znuABC<\/jats:italic>. Moreover, the MerR-type regulator, ZntR, controls the expression of the gene encoding the Zn exporter ZntA by binding directly to its promoter. Deletion of<jats:italic>zur<\/jats:italic>or<jats:italic>zntR<\/jats:italic>alone did not result in increased zinc toxicity in the corresponding mutants; however, deletion of<jats:italic>zntA<\/jats:italic>led to increased sensitivity to Zn but not to other metals, such as Cu and Ni, suggesting that ZntA is a Zn-specific exporter. Strikingly, deletion of<jats:italic>zntR<\/jats:italic>resulted in significant attenuation of<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>in a mouse model of chronic infection, and subsequent experiments revealed that overexpression of<jats:italic>zntA<\/jats:italic>in the<jats:italic>zntR<\/jats:italic>mutant is the molecular basis for its decreased virulence.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>The importance of zinc uptake for<jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>pathogenesis has been demonstrated previously, but to date, there has been no description of how overall zinc homeostasis is maintained and genetically controlled in the brucellae. The present work defines the predominant zinc export system, as well as the key genetic regulators of both zinc uptake and export in<jats:named-content content-type=\"genus-species\">Brucella abortus<\/jats:named-content>. Moreover, the data show the importance of precise coordination of the zinc homeostasis systems as disregulation of some elements of these systems leads to the attenuation of<jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>virulence in a mouse model. Overall, this study advances our understanding of the essential role of zinc in the pathogenesis of intracellular bacteria.<\/jats:p>","DOI":"10.1128\/jb.02543-14","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T08:16:48Z","timestamp":1424247408000},"page":"1582-1591","source":"Crossref","is-referenced-by-count":35,"title":["Coordinated Zinc Homeostasis Is Essential for the Wild-Type Virulence of Brucella abortus"],"prefix":"10.1128","volume":"197","author":[{"given":"Lauren M.","family":"Sheehan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Budnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"R. 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