ArticleJournal of bacteriology2015
Coordinated zinc homeostasis is essential for the wild-type virulence of Brucella abortus.
Article in Journal of bacteriology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- A previously uncharacterized Fur-family metalloregulator integrates iron- and manganese-sensing to control virulence gene regulatory networks in Brucella.Scientific reports · 2025Article
- ZntR is a critical regulator for zinc homeostasis and involved in pathogenicity inMicrobiology spectrum · 2025Article
- Brucellosis: Bacteriology, pathogenesis, epidemiology and role of the metallophores in virulence: a review.Frontiers in cellular and infection microbiology · 2025Review
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.Chemical reviews · 2024Review
- Article
- A bioinformatic analysis of zinc transporters in intestinal Lactobacillaceae.Metallomics : integrated biometal science · 2023Article
- Scanning iron response regulator binding sites using Dap-seq in the Brucella genome.PLoS neglected tropical diseases · 2023Article
- Characterization of three predicted zinc exporters inFrontiers in veterinary science · 2023Article
- A Novel Zinc Exporter CtpG Enhances Resistance to Zinc Toxicity and Survival in Mycobacterium bovis.Microbiology spectrum · 2022Article
- Article
- Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants.BMC microbiology · 2021Article
- Uncovering the Hidden Credentials ofMicrobiology and molecular biology reviews : MMBR · 2021Review
- Zinc uptake system ZnuACB is essential for maintaining pathogenic phenotype of F4acVeterinary research · 2020Article
- A central role for the transcriptional regulator VtlR in small RNA-mediated gene regulation in Agrobacterium tumefaciens.Scientific reports · 2020Article
- Defining the regulatory mechanism of NikR, a nickel-responsive transcriptional regulator, in Brucella abortus.Microbiology (Reading, England) · 2018Article
- Bacterial zinc uptake regulator proteins and their regulons.Biochemical Society transactions · 2018Review
- Zinc Acquisition Mechanisms Differ between Environmental and Virulent Francisella Species.Journal of bacteriology · 2018Article
- Proline utilization system is required for infection by the pathogenic α-proteobacterium Brucella abortus.Microbiology (Reading, England) · 2017Article
- Zinc-Dependent Transcriptional Regulation inFrontiers in microbiology · 2017Article
- A dual-targeting approach to inhibit Brucella abortus replication in human cells.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledMetal 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 Zn-sensing 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.
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