Severe Zinc Depletion of Escherichia coli

Graham, Alison I.; Hunt, Stuart; Stokes, Sarah L.; Bramall, Neil; Bunch, Josephine; Cox, Alan G.; McLeod, Cameron W.; Poole, Robert K.

doi:10.1074/jbc.m109.001503

Cited by 124 publications

(104 citation statements)

References 57 publications

(64 reference statements)

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“…The downstream znuB and znuC expression levels consequently are not as high. Notably, modest upregulation of znuB and/or znuC in the ⌬zur::Km mutant or under Zn-limiting conditions has been reported previously for other organisms (39,41,42,44,48).…”

Section: Discussionmentioning

confidence: 88%

“…Some of the genes found to be Zur regulated in A. baumannii have homologs shown to be Zur or Zn regulated in other bacteria, largely those genes involved in metal homeostasis (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). These include znuA, znuB, znuC, znuD1, znuD2, rpmE2, czcD, and a gene encoding a putative siderophore receptor, A1S_0092.…”

Section: Discussionmentioning

confidence: 99%

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Acinetobacter baumannii Response to Host-Mediated Zinc Limitation Requires the Transcriptional Regulator Zur

et al. 2014

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Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia in intensive care units, and the increasing rates of antibiotic resistance make treating these infections challenging. Consequently, there is an urgent need to develop new antimicrobials to treat A. baumannii infections. One potential therapeutic option is to target bacterial systems involved in maintaining appropriate metal homeostasis, processes that are critical for the growth of pathogens within the host. The A. baumannii inner membrane zinc transporter ZnuABC is required for growth under low-zinc conditions and for A. baumannii pathogenesis. The expression of znuABC is regulated by the transcriptional repressor Zur. To investigate the role of Zur during the A. baumannii response to zinc limitation, a zur deletion mutant was generated, and transcriptional changes were analyzed using RNA sequencing. A number of Zur-regulated genes were identified that exhibit increased expression both when zur is absent and under lowzinc conditions, and Zur binds to predicted Zur box sequences of several genes affected by zinc levels or the zur mutation. Furthermore, the zur mutant is impaired for growth in the presence of both high and low zinc levels compared to wild-type A. baumannii. Finally, the zur mutant exhibits a defect in dissemination in a mouse model of A. baumannii pneumonia, establishing zinc sensing as a critical process during A. baumannii infection. These results define Zur-regulated genes within A. baumannii and demonstrate a requirement for Zur in the A. baumannii response to the various zinc levels experienced within the vertebrate host.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Acinetobacter baumannii Response to Host-Mediated Zinc Limitation Requires the Transcriptional Regulator Zur

et al. 2014

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“…It was proposed that large amounts of the binding lipoprotein MtsA at the cell surface could serve as a reservoir of metal cations while awaiting contact with the less available MtsBC proteins embedded in the membrane (21). Another gene involved in Zn(II) binding, the E. coli znuA gene, which is adjacent to but divergent from the znuBC operon, is 2-fold more upregulated than the znuB and znuC genes under Zn(II) depletion conditions (18). Interestingly, the adcA genes in Streptococcus mutans and S. pyogenes are orphan genes (29,38).…”

Section: Discussionmentioning

confidence: 99%

“…Bacterial responses to zinc have been studied by genome-wide transcriptional analyses in Escherichia coli (8,26), Bacillus subtilis (31), and Streptococcus pneumoniae (24), showing altered expression of numerous genes implicated in tolerance for and efflux of zinc and other metals, and also in general stress resistance. Conversely, zinc depletion in E. coli regulates a small number of genes involved in high-affinity zinc binding and uptake or encoding zinc-independent ribosomal proteins (18).…”

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confidence: 99%

Lactococcus lactis ZitR Is a Zinc-Responsive Repressor Active in the Presence of Low, Nontoxic Zinc Concentrations In Vivo

et al. 2011

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In the family Streptococcaceae, the genes encoding zinc ABC uptake systems (called zit or adc) are regulated by a coencoded MarR family member (i.e., ZitR or AdcR), whereas in the great majority of bacteria, these genes are regulated by Zur, the Fur-like zinc-responsive repressor. We studied the zit operon from Lactococcus lactis and its regulation in response to Zn(II) in vivo. zit transcription is repressed by Zn(II) in a wide concentration range starting from nontoxic micromolar levels and is derepressed at nanomolar concentrations. The level of zit promoter downregulation by environmental Zn(II) is correlated with the intracellular zinc content. The helix-turn-helix domain of ZitR is required for downregulation. In vitro, the purified protein is a dimer that complexes up to two zinc ligands per monomer and specifically binds two intact palindromic operator sites overlapping the ؊35 and ؊10 boxes of the zit promoter. DNA binding is abolished by the chelator EDTA or TPEN and fully restored by Zn(II) addition, indicating that the active repressor complexes Zn(II) with high affinity. These results suggest that derepression under starvation conditions could be an essential emergency mechanism for preserving Zn(II) homeostasis by uptake; under Zn(II)-replete conditions, the function of ZitR repression could be to help save energy rather than to avoid Zn(II) toxicity. The characterization of a MarR family zinc-responsive repressor in this report gives insight into the way Streptococcaceae efficiently adapt to Zn(II) fluctuations in their diverse ecological niches.

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“…ZnuA is a periplasmic protein that binds zinc and transfers it to the membrane permease ZnuB and the ATPase ZnuC (15). The ZinT protein is a periplasmic zinc-binding protein (18)(19)(20)(21) that has been shown to directly interact with and assist ZnuABC in transporting zinc in Salmonella enterica (22,23).…”

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confidence: 99%

Agrobacterium tumefaciens Zur Regulates the High-Affinity Zinc Uptake System TroCBA and the Putative Metal Chaperone YciC, along with ZinT and ZnuABC, for Survival under Zinc-Limiting Conditions

Chaoprasid

Dokpikul

Johnrod

et al. 2016

Appl Environ Microbiol

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Agrobacterium tumefaciens has a cluster of genes (Atu3178, Atu3179, and Atu3180) encoding an ABC-type transporter, here named troA, troB, and troC, respectively, which is shown here to be a zinc-specific uptake system. Reverse transcription (RT)-PCR analysis confirmed that troA, troB, and troC are cotranscribed, with troC as the first gene of the operon. The yciC (Atu3181) gene is transcribed in the opposite orientation to that of the troCBA operon and belongs to a metal-binding GTPase family. Expression of troCBA and yciC was inducible under zinc-limiting conditions and was controlled by the zinc uptake regulator, Zur. Compared to the wild type, the mutant strain lacking troC was hypersensitive to a metal chelator, EDTA, and the phenotype could be rescued by the addition of zinc, while the strain with a single yciC mutation showed no phenotype. However, yciC was important for survival under zinc limitation when either troC or zinT was inactivated. The periplasmic zinc-binding protein, ZinT, could not function when TroC was inactivated, suggesting that ZinT may interact with TroCBA in zinc uptake. Unlike many other bacteria, the ABC-type transporter ZnuABC was not the major zinc uptake system in A. tumefaciens. However, the important role of A. tumefaciens ZnuABC was revealed when TroCBA was impaired. The strain containing double mutations in the znuA and troC genes exhibited a growth defect in minimal medium. A. tumefaciens requires cooperation of zinc uptake systems and zinc chaperones, including TroCBA, ZnuABC, ZinT, and YciC, for survival under a wide range of zinc-limiting conditions. IMPORTANCEBoth host and pathogen battle over access to essential metals, including zinc. In low-zinc environments, physiological responses that make it possible to acquire enough zinc are important for bacterial survival and could determine the outcome of hostpathogen interactions. A. tumefaciens was found to operate a novel pathway for zinc uptake in which ZinT functions in concert with the high-affinity zinc importer TroCBA. Zinc is an essential metal for bacteria because it is required for the functions of many enzymes and proteins (1, 2). However, zinc overload is toxic to cells (3-7). Bacteria have mechanisms to maintain zinc homeostasis via the coordinated response of genes involved in zinc uptake, efflux, and storage (8-13). The zinc uptake regulator Zur is a transcriptional regulator belonging to the Fur family and functions as a repressor of zinc uptake genes, including znuABC and zinT (10). To prevent excessive amounts of zinc in cells under high-zinc conditions, Zur uses Zn 2ϩ as its cofactor to bind to a conserved AT-rich sequence, called the Zur box (14), found in the promoter region of the zinc uptake genes, leading to inhibition of gene expression (15)(16)(17). ZnuA is a periplasmic protein that binds zinc and transfers it to the membrane permease ZnuB and the ATPase ZnuC (15). The ZinT protein is a periplasmic zinc-binding protein (18-21) that has been shown to directly interact with and assist ZnuABC i...

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Severe Zinc Depletion of Escherichia coli

Abstract: N,N,N,N-tetrakis(2-pyridylmethyl)ethylenediamine.

Cited by 124 publications

References 57 publications

Acinetobacter baumannii Response to Host-Mediated Zinc Limitation Requires the Transcriptional Regulator Zur

Acinetobacter baumannii Response to Host-Mediated Zinc Limitation Requires the Transcriptional Regulator Zur

Lactococcus lactis ZitR Is a Zinc-Responsive Repressor Active in the Presence of Low, Nontoxic Zinc Concentrations In Vivo

Agrobacterium tumefaciens Zur Regulates the High-Affinity Zinc Uptake System TroCBA and the Putative Metal Chaperone YciC, along with ZinT and ZnuABC, for Survival under Zinc-Limiting Conditions

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