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dc.contributorVirginia Techen_US
dc.contributor.authorSheehan, Lauren M.en_US
dc.contributor.authorBudnick, James A.en_US
dc.contributor.authorRoop, R. Martin, IIen_US
dc.contributor.authorCaswell, Clayton C.en_US
dc.date.accessioned2015-11-28T21:53:47Z
dc.date.available2015-11-28T21:53:47Z
dc.date.issued2015-02-17en_US
dc.identifier.citationSheehan, Lauren M., et al. (2015). Coordinated Zinc Homeostasis Is Essential for the Wild-Type Virulence of Brucella abortus. Journal of Bacteriology, 197(9), 1582-1591. doi:10.1128/jb.02543-14en_US
dc.identifier.issn0021-9193en_US
dc.identifier.urihttp://hdl.handle.net/10919/64213
dc.description.abstractMetal 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 Brucella abortus; however, the capacity of Brucella 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 Znsensing Fur family transcriptional regulator, Zur, by direct interactions between Zur and the promoter region of znuABC. 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 zur or zntR alone did not result in increased zinc toxicity in the corresponding mutants; however, deletion of zntA 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 zntR resulted in significant attenuation of B. abortus in a mouse model of chronic infection, and subsequent experiments revealed that overexpression of zntA in the zntR mutant is the molecular basis for its decreased virulence. IMPORTANCE The importance of zinc uptake for Brucella 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 Brucella abortus. 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 Brucella virulence in a mouse model. Overall, this study advances our understanding of the essential role of zinc in the pathogenesis of intracellular bacteria.en_US
dc.description.sponsorshipVirginia-Maryland College of Veterinary Medicineen_US
dc.description.sponsorshipVirginia Tech. Fralin Life Science Instituteen_US
dc.description.sponsorshipAI48499en_US
dc.description.sponsorshipAI63516en_US
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseasesen_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.titleCoordinated Zinc Homeostasis Is Essential for the Wild-Type Virulence of Brucella abortus
dc.typeArticle - Refereed
dc.contributor.departmentVirginia Tech. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseasesen_US
dc.identifier.urlhttp://jb.asm.org/content/197/9/1582en_US
dc.date.accessed2015-10-01en_US
dc.title.serialJournal of Bacteriologyen_US
dc.identifier.doihttps://doi.org/10.1128/jb.02543-14
dc.type.dcmitypeText


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