Dataset Information

Molecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis.

ABSTRACT: Bacteria respond dynamically to the changes in zinc availability. Repression by the Bacillus subtilis transcription factor Zur requires Zn(II), which binds with negative cooperativity to two regulatory sites per dimer to form, sequentially, Zur2:Zn3 and Zur2:Zn4 forms of the repressor. Here we show that, as cells transition from zinc sufficiency to deficiency, operons regulated by Zur are derepressed in three distinct waves. The first includes the alternative RpmEB(L31*) and RpmGC(L33*) ribosomal proteins, which mobilize zinc from the ribosome, whereas the second includes the ZnuACB uptake system and the YciC metallochaperone. Finally, as zinc levels decrease further, the Zur2:Zn3 form loses Zn(II) leading to derepression of RpsNB(S14*) and FolE2, which allow continued ribosome assembly and folate synthesis, respectively. We infer that zinc mobilization from intracellular zinc stores takes priority over energy-dependent import, and our results link the biochemistry of zinc sensing by Zur to the molecular logic of the zinc deprivation response.

SUBMITTER: Shin JH

PROVIDER: S-EPMC5007448 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Molecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis.

Shin Jung-Ho JH Helmann John D JD

Nature communications 20160826

Bacteria respond dynamically to the changes in zinc availability. Repression by the Bacillus subtilis transcription factor Zur requires Zn(II), which binds with negative cooperativity to two regulatory sites per dimer to form, sequentially, Zur2:Zn3 and Zur2:Zn4 forms of the repressor. Here we show that, as cells transition from zinc sufficiency to deficiency, operons regulated by Zur are derepressed in three distinct waves. The first includes the alternative RpmEB(L31*) and RpmGC(L33*) ribosoma ...[more]

PMID: 27561249

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Project description:We assessed changes in gene expression in response to zinc availability for the human pathogen Corynebacterium diphtheriae. Expression profiles of wild-type C. diphtheriae strain 1737 grown in semi-defined metal-poor media (mPGT) without and with 5 µM zinc chloride supplementation were compared; the expression profile of wild-type C. diphtheriae strain 1737 in zinc-replete conditions was also compared against an isogenic Δzur mutant grown in zinc-replete conditions. Three biological replicates were prepared by isolating total RNA from mid-logarithmic growth cultures and eleven genes (dip0013, dip0093, dip0173, dip0438, dip1087, dip1486, dip1724, dip2114, dip2128, dip2162, and dip2325) were assessed by real-time PCR to validate the array results. (Abstract) Corynebacterium diphtheriae is a Gram-positive bacterial pathogen and the causative agent of diphtheria, a severe disease of the upper respiratory tract of humans. Factors required for C. diphtheriae to survive in the human host are not well defined, but likely include the acquisition of essential metals such as zinc. In C. diphtheriae, zinc-responsive global gene regulation is controlled by the Zinc Uptake Regulator (Zur), a member of the Fur-family of transcriptional regulators. In this study, we use transcriptomics to identify zinc-regulated genes in C. diphtheriae by comparing gene expression of a wild-type strain grown without and with zinc supplementation. Zur-regulated genes were identified by comparing wild-type gene expression with that of an isogenic zur mutant. We observed zinc repression of several putative surface proteins, the heme efflux system hrtBA, various ABC transporters, and the non-ribosomal peptide synthetase/polyketide synthase cluster sidAB. Furthermore, increased gene expression in response to zinc was observed for the alcohol dehydrogenase, adhA. Zinc and Zur regulation were confirmed for several genes by complementing the zur deletion and subsequent qPCR analysis. We used MEME to predict Zur binding sites within the promoter regions of zinc- and Zur-regulated genes, and verified Zur binding by electrophoretic mobility shift assays. Additionally, we characterized cztA (dip1101), which encodes a putative cobalt/zinc/cadmium efflux family protein. Deletion of cztA results in increased sensitivity to zinc, but not to cobalt or cadmium. This study advances our knowledge of changes to Zur-dependent global gene expression in response to zinc in C. diphtheriae. The identification of zinc-regulated ABC transporters herein will facilitate future studies to characterize zinc transport in C. diphtheriae.

Dataset Information

Molecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis.

Publications

Molecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis.

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