scholarly journals Behind the shield of Czc: ZntR controls expression of the gene for the zinc-exporting P-type ATPase ZntA in Cupriavidus metallidurans

2021 ◽  
Author(s):  
Vladislava Schulz ◽  
Christopher Schmidt-Vogler ◽  
Phillip Strohmeyer ◽  
Stefanie Weber ◽  
Daniel Kleemann ◽  
...  
Keyword(s):  
Cadmium Concentration ◽  
Zinc Content ◽  
Metal Resistance ◽  
Zinc Uptake ◽  
Uptake System ◽  
Zinc Ions ◽  
Cupriavidus Metallidurans ◽  
Zinc Concentrations ◽  
Main Regulator ◽  
Cellular Zinc

In the metallophilic beta-proteobacterium Cupriavidus metallidurans, the plasmid-encoded Czc metal homeostasis system adjusts the periplasmic zinc, cobalt and cadmium concentration, which influences subsequent uptake of these metals into the cytoplasm. Behind this shield, the PIB2-type APTase ZntA is responsible for removal of surplus cytoplasmic zinc ions, thereby providing a second level of defense against toxic zinc concentrations. ZntA is the counterpart to the Zur-regulated zinc uptake system ZupT and other import systems; however, the regulator of zntA expression was unknown. The chromid-encoded zntA gene is adjacent to the genes czcI2C2B2’, which are located on the complementary DNA strand and transcribed from a common promoter region. These genes encode homologs of plasmid pMOL30-encoded Czc components. Candidates for possible regulators of zntA were identified and subsequently tested: CzcI, CzcI2, and the MerR-type gene products of the locus tags Rmet_2302, Rmet_0102, Rmet_3456. This led to the identification of Rmet_3456 as ZntR, the main regulator of zntA expression. Moreover, both CzcIs decreased Czc-mediated metal resistance, possibly to avoid “over-excretion” of periplasmic zinc ions, which could result in zinc starvation due to diminished zinc uptake into the cytoplasm. Rmet_2302 was identified as CadR, the regulator of the cadA gene for an important cadmium-exporting PIB2-type ATPase, which provides another system for removal of cytoplasmic zinc and cadmium. Rmet_0102 was not involved in regulation of the metal resistance systems examined here. Thus, ZntR forms a complex regulatory network with CadR, Zur and the CzcIs. Moreover, these discriminating regulatory proteins assign the efflux systems to their particular function. Importance Zinc is an essential metal for numerous organisms from humans to bacteria. The transportome of zinc uptake and efflux systems controls the overall cellular composition and zinc content in a double feed-back loop. Zinc starvation mediates, via the Zur regulator, an up-regulation of the zinc import capacity via the ZIP-type zinc importer ZupT and an amplification of zinc storage capacity, which together raise the cellular zinc content again. On the other hand, an increasing zinc content leads to ZntR-mediated up-regulation of the zinc efflux system ZntA, which decreases the zinc content. Together, the Zur regulon components and ZntR/ZntA balance the cellular zinc content under both high external zinc concentrations and zinc starvation conditions.

scholarly journals Loss of Zhf and the tightly regulated zinc-uptake system SpZrt1 inSchizosaccharomyces pombereveals the delicacy of cellular zinc balance

2008 ◽  
Vol 8 (6) ◽  
pp. 883-896 ◽  
Author(s):  
Annegret Boch ◽  
Aleksandra Trampczynska ◽  
Claudia Simm ◽  
Nadine Taudte ◽  
Ute Krämer ◽  
...  
Keyword(s):  
Zinc Uptake ◽  
Uptake System ◽  
Cellular Zinc ◽  
Zinc Balance

The effect of chlorsulfuron and diclofop-methyl on the uptake and utilization of zinc by wheat

1992 ◽  
Vol 43 (1) ◽  
pp. 59 ◽  
Author(s):  
LD McLay ◽  
AD Robson
Keyword(s):  
Zinc Content ◽  
Zinc Uptake ◽  
Root Weight ◽  
Active Ingredients ◽  
Zinc Concentrations ◽  
Zinc Diffusion ◽  
Shoot Weight

The effects of the herbicides Hoegrass and Glean on the uptake of zinc by wheat were examined in two glasshouse experiments. Application of the active ingredients chlorsulfuron and diclofop-methyl decreased shoot weight, root weight and zinc uptake similarly to the herbicides Glean and Hoegrass. It can therefore be concluded that the effects of Hoegrass and Glean on zinc uptake in wheat can be attributed to these active ingredients and not to other constituents of the commercial herbicide preparations. Effects of chlorsulfuron on zinc uptake in soil were different from those obtained in solution. In soil, chlorsulfuron decreased both zinc concentrations in the youngest emerged blade and zinc content of shoots, while in solution where uptake is not likely to be limited by the rate of zinc diffusion to sites of absorption, there were no significant effects on zinc uptake. However, in both soil and solution, shoot and root weights were decreased by herbicide, particularly at low rates of zinc supply. Roots were shorter and thicker when herbicide concentrations in solution were increased.

The human zinc transporter SLC39A8 (Zip8) is critical in zinc-mediated cytoprotection in lung epithelia

2008 ◽  
Vol 294 (6) ◽  
pp. L1127-L1136 ◽  
Author(s):  
Beth Besecker ◽  
Shengying Bao ◽  
Barbara Bohacova ◽  
Audrey Papp ◽  
Wolfgang Sadee ◽  
...  
Keyword(s):  
Cell Survival ◽  
Zinc Content ◽  
Zinc Transporters ◽  
Rt Pcr ◽  
Intracellular Zinc ◽  
Inflammatory Stress ◽  
Tnf Α ◽  
Zinc Concentrations ◽  
Interfering Rna ◽  
Cellular Zinc

Zinc is an essential micronutrient and cytoprotectant involved in the host response to inflammatory stress. We tested whether zinc transporters, the critical regulators that maintain intracellular zinc concentrations, play a role in cell survival, particularly in lung epithelia, during inflammation. Initially, mRNA transcripts were quantitatively measured by RT-PCR for all known human zinc transporters, including 14 importers (SLC39A1–14) and 10 exporters (SLC30A1–10), in primary human lung epithelia obtained from multiple human donors and BEAS-2B cell cultures under baseline and TNF-α-stimulated conditions. While many zinc transporters were constitutively expressed, only SLC39A8 (Zip8) mRNA was strongly induced by TNF-α. Endogenous Zip8 protein was not routinely detected under baseline conditions. In sharp contrast, TNF-α induced the expression of a glycosylated protein that translocated to the plasma membrane and mitochondria. Increased Zip8 expression resulted in an increase in intracellular zinc content and coincided with cell survival in the presence of TNF-α. Inhibition of Zip8 expression using a short interfering RNA probe reduced cellular zinc content and impaired mitochondrial function in response to TNF-α, resulting in loss of cell viability. These data are the first to characterize human Zip8 and remarkably demonstrate that upregulation of Zip8 is sufficient to protect lung epithelia against TNF-α-induced cytotoxicity. We conclude that Zip8 is unique, relative to other Zip proteins, by functioning as an essential zinc importer at the onset of inflammation, thereby facilitating cytoprotection within the lung.

scholarly journals The Components of the Unique Zur Regulon of Cupriavidus metallidurans Mediate Cytoplasmic Zinc Handling

2017 ◽  
Vol 199 (21) ◽  
Author(s):  
Lucy Bütof ◽  
Christopher Schmidt-Vogler ◽  
Martin Herzberg ◽  
Cornelia Große ◽  
Dietrich H. Nies
Keyword(s):  
Consensus Sequence ◽  
Regulatory Region ◽  
Metal Resistance ◽  
Resistant Bacterium ◽  
Zinc Homeostasis ◽  
Mineral Salts ◽  
Content Type ◽  
Zip Family ◽  
Cupriavidus Metallidurans ◽  
Zinc Concentrations

ABSTRACT Zinc is an essential trace element, yet it is toxic at high concentrations. In the betaproteobacterium Cupriavidus metallidurans, the highly efficient removal of surplus zinc from the periplasm is responsible for the outstanding metal resistance of the organism. Rather than having a typical Zur-dependent, high-affinity ATP-binding cassette transporter of the ABC protein superfamily for zinc uptake at low concentrations, C. metallidurans has the secondary zinc importer ZupT of the zinc-regulated transporter, iron-regulated transporter (ZRT/IRT)-like protein (ZIP) family. It is important to understand, therefore, how this zinc-resistant bacterium copes with exposure to low zinc concentrations. Members of the Zur regulon in C. metallidurans were identified by comparing the transcriptomes of a Δzur mutant and its parent strain. The consensus sequence of the Zur-binding box was derived for the zupTp promoter-regulatory region by use of a truncation assay. The motif was used to predict possible Zur boxes upstream of Zur regulon members. The binding of Zur to these boxes was confirmed. Two Zur boxes upstream of the cobW 1 gene, encoding a putative zinc chaperone, proved to be required for complete repression of cobW 1 and its downstream genes in cells cultivated in mineral salts medium. A Zur box upstream of each of zur-cobW 2, cobW 3, and zupT permitted both low expression levels of these genes and their upregulation under conditions of zinc starvation. This demonstrates a compartmentalization of zinc homeostasis in C. metallidurans, where the periplasm is responsible for the removal of surplus zinc, cytoplasmic components are responsible for the management of zinc as an essential cofactor, and the two compartments are connected by ZupT. IMPORTANCE Elucidating zinc homeostasis is necessary for understanding both host-pathogen interactions and the performance of free-living bacteria in their natural environments. Escherichia coli acquires zinc under conditions of low zinc concentrations via the Zur-controlled ZnuABC importer of the ABC superfamily, and this was also the paradigm for other bacteria. In contrast, the heavy-metal-resistant bacterium C. metallidurans achieves high tolerance to zinc through sophisticated zinc handling and efflux systems operating on periplasmic zinc ions, so that removal of surplus zinc is a periplasmic feature in this bacterium. It is shown here that this process is augmented by the management of zinc by cytoplasmic zinc chaperones, whose synthesis is controlled by the Zur regulator. This demonstrates a new mechanism, involving compartmentalization, for organizing zinc homeostasis.

scholarly journals Adaptation of Cupriavidus metallidurans CH34 to Toxic Zinc Concentrations Involves an Uncharacterized ABC-Type Transporter

2021 ◽  
Vol 9 (2) ◽  
pp. 309
Author(s):  
Rob Van Houdt ◽  
Joachim Vandecraen ◽  
Natalie Leys ◽  
Pieter Monsieurs ◽  
Abram Aertsen
Keyword(s):  
Abc Transporter ◽  
Rhizobium Leguminosarum ◽  
Constitutive Expression ◽  
Metal Resistance ◽  
Cadmium Resistance ◽  
Gene Encoding ◽  
Cupriavidus Metallidurans Ch34 ◽  
Cupriavidus Metallidurans ◽  
High Zinc ◽  
Zinc Concentrations

Cupriavidus metallidurans CH34 is a well-studied metal-resistant β-proteobacterium and contains a battery of genes participating in metal metabolism and resistance. Here, we generated a mutant (CH34ZnR) adapted to high zinc concentrations in order to study how CH34 could adaptively further increase its resistance against this metal. Characterization of CH34ZnR revealed that it was also more resistant to cadmium, and that it incurred seven insertion sequence-mediated mutations. Among these, an IS1088 disruption of the glpR gene (encoding a DeoR-type transcriptional repressor) resulted in the constitutive expression of the neighboring ATP-binding cassette (ABC)-type transporter. GlpR and the adjacent ABC transporter are highly similar to the glycerol operon regulator and ATP-driven glycerol importer of Rhizobium leguminosarum bv. viciae VF39, respectively. Deletion of glpR or the ABC transporter and complementation of CH34ZnR with the parental glpR gene further demonstrated that loss of GlpR function and concomitant derepression of the adjacent ABC transporter is pivotal for the observed resistance phenotype. Importantly, addition of glycerol, presumably by glycerol-mediated attenuation of GlpR activity, also promoted increased zinc and cadmium resistance in the parental CH34 strain. Upregulation of this ABC-type transporter is therefore proposed as a new adaptation route towards metal resistance.

scholarly journals Functional Analysis of the Bacillus subtilis Zur Regulon

2002 ◽  
Vol 184 (23) ◽  
pp. 6508-6514 ◽  
Author(s):  
Ahmed Gaballa ◽  
Tao Wang ◽  
Rick W. Ye ◽  
John D. Helmann
Keyword(s):  
Bacillus Subtilis ◽  
Metal Ion ◽  
Dna Microarrays ◽  
Optimal Growth ◽  
Zinc Uptake ◽  
Uptake System ◽  
Mobility Shift ◽  
Transport Pathway ◽  
Dnase I Footprinting ◽  
Transporter Family

ABSTRACT The Bacillus subtilis zinc uptake repressor (Zur) regulates genes involved in zinc uptake. We have used DNA microarrays to identify genes that are derepressed in a zur mutant. In addition to members of the two previously identified Zur-regulated operons (yciC and ycdHI-yceA), we identified two other genes, yciA and yciB, as targets of Zur regulation. Electrophoretic mobility shift experiments demonstrated that all three operons are direct targets of Zur regulation. Zur binds to an ∼28-bp operator upstream of the yciA gene, as judged by DNase I footprinting, and similar operator sites are found preceding each of the previously described target operons, yciC and ycdHI-yceA. Analysis of a yciA-lacZ fusion indicates that this operon is induced under zinc starvation conditions and derepressed in the zur mutant. Phenotypic analyses suggest that the YciA, YciB, and YciC proteins may function as part of the same Zn(II) transport pathway. Mutation of yciA or yciC, singly or in combination, had little effect on growth of the wild-type strain but significantly impaired the growth of the ycdH mutant under conditions of zinc limitation. Since the YciA, YciB, and YciC proteins are not obviously related to any known transporter family, they may define a new class of metal ion uptake system. Mutant strains lacking all three identified zinc uptake systems (yciABC, ycdHI-yceA, and zosA) are dependent on micromolar levels of added zinc for optimal growth.

scholarly journals Cupriavidus metallidurans Strains with Different Mobilomes and from Distinct Environments Have Comparable Phenomes

Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 507 ◽  
Author(s):  
Rob Van Houdt ◽  
Ann Provoost ◽  
Ado Van Assche ◽  
Natalie Leys ◽  
Bart Lievens ◽  
...  
Keyword(s):  
Genomic Island ◽  
Space Station ◽  
Nutrient Utilization ◽  
Metal Resistance ◽  
Human Infection ◽  
Abietane Diterpenoids ◽  
Cupriavidus Metallidurans ◽  
Mobile Gene ◽  
Phenotype Microarrays ◽  
The Impact

Cupriavidus metallidurans has been mostly studied because of its resistance to numerous heavy metals and is increasingly being recovered from other environments not typified by metal contamination. They host a large and diverse mobile gene pool, next to their native megaplasmids. Here, we used comparative genomics and global metabolic comparison to assess the impact of the mobilome on growth capabilities, nutrient utilization, and sensitivity to chemicals of type strain CH34 and three isolates (NA1, NA4 and H1130). The latter were isolated from water sources aboard the International Space Station (NA1 and NA4) and from an invasive human infection (H1130). The mobilome was expanded as prophages were predicted in NA4 and H1130, and a genomic island putatively involved in abietane diterpenoids metabolism was identified in H1130. An active CRISPR-Cas system was identified in strain NA4, providing immunity to a plasmid that integrated in CH34 and NA1. No correlation between the mobilome and isolation environment was found. In addition, our comparison indicated that the metal resistance determinants and properties are conserved among these strains and thus maintained in these environments. Furthermore, all strains were highly resistant to a wide variety of chemicals, much broader than metals. Only minor differences were observed in the phenomes (measured by phenotype microarrays), despite the large difference in mobilomes and the variable (shared by two or three strains) and strain-specific genomes.

The Effect of Synchronous Moulting on Body Copper and Zinc Concentrations in Four Species of Talitrid Amphipods (Crustacea)

1991 ◽  
Vol 71 (2) ◽  
pp. 481-488 ◽  
Author(s):  
J. M. Weeks ◽  
P. G. Moore
Keyword(s):  
Tidal Cycle ◽  
Zinc Content ◽  
Lunar Cycle ◽  
Moult Cycle ◽  
Metal Concentrations ◽  
Total Copper ◽  
Copper And Zinc ◽  
Talitrus Saltator ◽  
Zinc Concentrations ◽  
New Moon

Analysis of the total copper and zinc content of four species of talitrid amphipods, Orchestia gammarellus, O. mediterranea, Talitrus saltator and Talorchestia deshayesii throughout a complete spring/neap tidal cycle failed to reveal any significant effects of moulting upon body copper or zinc in any species. Moulting was synchronized to the lunar cycle only in T. saltator, taking place 5–7 days prior to a new moon. The fact that no significant changes in body metal concentrations took place with the moult cycle is discussed in relation to the use of talitrid amphipods in copper and zinc biomonitoring programmes.

Is Spina Bifida in Man Linked to a Genetic Defect of Cellular Zinc Uptake in Children ?

1988 ◽  
pp. 609-610 ◽  
Author(s):  
Alain Favier ◽  
Brigitte Dardelet ◽  
Marie-Jeanne Richard ◽  
Josiane Arnaud
Keyword(s):  
Spina Bifida ◽  
Genetic Defect ◽  
Zinc Uptake ◽  
Cellular Zinc

scholarly journals The zinc transporter ZnuABC is critical for the virulence of Chromobacterium violaceum and contributes to diverse zinc-dependent physiological processes

2021 ◽  
Author(s):  
Renato E. R. S. Santos ◽  
Waldir P. da Silva Júnior ◽  
Simone A. Harrison ◽  
Eric P Skaar ◽  
Walter J. Chazin ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Zinc Uptake ◽  
Chromobacterium Violaceum ◽  
Host Protein ◽  
Infection Model ◽  
Uptake System ◽  
Environmental Bacterium ◽  
Mouse Infection Model ◽  
Synthetic Metal

Chromobacterium violaceum is a ubiquitous environmental bacterium that causes sporadic life-threatening infections in humans. How C. violaceum acquires zinc to colonize environmental and host niches is unknown. In this work, we demonstrated that C. violaceum employs the zinc uptake system ZnuABC to overcome zinc limitation in the host, ensuring the zinc supply for several physiological demands. Our data indicated that the C. violaceum ZnuABC transporter is encoded in a zur-CV_RS15045-CV_RS15040-znuCBA operon. This operon was repressed by the zinc uptake regulator Zur and derepressed in the presence of the host protein calprotectin (CP) and the synthetic metal chelator EDTA. A ΔznuCBA mutant strain showed impaired growth under these zinc-chelated conditions. Moreover, the deletion of znuCBA provoked a reduction in violacein production, swimming motility, biofilm formation, and bacterial competition. Remarkably, the ΔznuCBA mutant strain was highly attenuated for virulence in an in vivo mouse infection model and showed a low capacity to colonize the liver, grow in the presence of CP, and resist neutrophil killing. Overall, our findings demonstrate that ZnuABC is essential for C. violaceum virulence, contributing to subvert the zinc-based host nutritional immunity.

Sign in / Sign up

Export Citation Format

Share Document