scholarly journals Bacterial zinc uptake regulator proteins and their regulons

2018 ◽  
Vol 46 (4) ◽  
pp. 983-1001 ◽  
Author(s):  
Alevtina Mikhaylina ◽  
Amira Z. Ksibe ◽  
David J. Scanlan ◽  
Claudia A. Blindauer
Keyword(s):  
Intracellular Trafficking ◽  
Ribosomal Proteins ◽  
Pathogenic Bacteria ◽  
Transcriptional Regulators ◽  
Research Area ◽  
Essential Elements ◽  
Zinc Uptake ◽  
Zinc Homeostasis ◽  
Dna Binding Affinity ◽  
Zinc Uptake Regulator

All organisms must regulate the cellular uptake, efflux, and intracellular trafficking of essential elements, including d-block metal ions. In bacteria, such regulation is achieved by the action of metal-responsive transcriptional regulators. Among several families of zinc-responsive transcription factors, the ‘zinc uptake regulator’ Zur is the most widespread. Zur normally represses transcription in its zinc-bound form, in which DNA-binding affinity is enhanced allosterically. Experimental and bioinformatic searches for Zur-regulated genes have revealed that in many cases, Zur proteins govern zinc homeostasis in a much more profound way than merely through the expression of uptake systems. Zur regulons also comprise biosynthetic clusters for metallophore synthesis, ribosomal proteins, enzymes, and virulence factors. In recognition of the importance of zinc homeostasis at the host–pathogen interface, studying Zur regulons of pathogenic bacteria is a particularly active current research area.

Zinc Uptake Regulator (zur) Gene Involved in Zinc Homeostasis and Virulence of Xanthomonas oryzae pv. oryzae in Rice

2007 ◽  
Vol 54 (4) ◽  
pp. 307-314 ◽  
Author(s):  
Wanfeng Yang ◽  
Yan Liu ◽  
Lei Chen ◽  
Tongchun Gao ◽  
Baishi Hu ◽  
...  
Keyword(s):  
Zinc Uptake ◽  
Xanthomonas Oryzae ◽  
Zinc Homeostasis ◽  
Zinc Uptake Regulator

scholarly journals Functional Definition and Global Regulation of Zur, a Zinc Uptake Regulator in a Streptococcus suis Serotype 2 Strain Causing Streptococcal Toxic Shock Syndrome

2008 ◽  
Vol 190 (22) ◽  
pp. 7567-7578 ◽  
Author(s):  
Youjun Feng ◽  
Ming Li ◽  
Huimin Zhang ◽  
Beiwen Zheng ◽  
Huiming Han ◽  
...  
Keyword(s):  
Toxic Shock Syndrome ◽  
Streptococcus Suis ◽  
Gene Replacement ◽  
Zinc Uptake ◽  
Zinc Homeostasis ◽  
Differentially Expressed ◽  
Streptococcal Toxic Shock Syndrome ◽  
Toxic Shock ◽  
Physiological Tests ◽  
Zinc Uptake Regulator

ABSTRACT Zinc is an essential trace element for all living organisms and plays pivotal roles in various cellular processes. However, an excess of zinc is extremely deleterious to cells. Bacteria have evolved complex machineries (such as efflux/influx systems) to control the concentration at levels appropriate for the maintenance of zinc homeostasis in cells and adaptation to the environment. The Zur (zinc uptake regulator) protein is one of these functional members involved in the precise control of zinc homeostasis. Here we identified a zur homologue designated 310 from Streptococcus suis serotype 2, strain 05ZYH33, a highly invasive isolate causing streptococcal toxic shock syndrome. Biochemical analysis revealed that the protein product of gene 310 exists as a dimer form and carries zinc ions. An isogenic gene replacement mutant of gene 310, the Δ310 mutant, was obtained by homologous recombination. Physiological tests demonstrated that the Δ310 mutant is specifically sensitive to Zn2+, while functional complementation of the Δ310 mutant can restore its duration capability, suggesting that 310 is a functional member of the Zur family. Two-dimensional electrophoresis indicated that nine proteins in the Δ310 mutant are overexpressed in comparison with those in the wild type. DNA microarray analyses suggested that 121 genes in the Δ310 mutant are affected, of which 72 genes are upregulated and 49 are downregulated. The transcriptome of S. suis serotype 2 with high Zn2+ concentrations also showed 117 differentially expressed genes, with 71 upregulated and 46 downregulated. Surprisingly, more than 70% of the genes differentially expressed in the Δ310 mutant were the same as those in S. suis serotype 2 that were differentially expressed in response to high Zn2+ concentration, consistent with the notion that 310 is involved in zinc homeostasis. We thus report for the first time a novel zinc-responsive regulator, Zur, from Streptococcus suis serotype 2.

scholarly journals Control of zinc homeostasis in Agrobacterium tumefaciens via zur and the zinc uptake genes znuABC and zinT

Microbiology ◽  
2014 ◽  
Vol 160 (11) ◽  
pp. 2452-2463 ◽  
Author(s):  
Sakkarin Bhubhanil ◽  
Panida Sittipo ◽  
Paweena Chaoprasid ◽  
Sumontha Nookabkaew ◽  
Rojana Sukchawalit ◽  
...  
Keyword(s):  
Agrobacterium Tumefaciens ◽  
Dominant Role ◽  
Zinc Content ◽  
Zinc Uptake ◽  
Zinc Homeostasis ◽  
Dependent Manner ◽  
Transporter Family ◽  
Zinc Depletion ◽  
Zinc Uptake Regulator ◽  
Dose Dependent

The Agrobacterium tumefaciens zinc uptake regulator (Zur) was shown to negatively regulate the zinc uptake genes znuABC, encoding a zinc transport system belonging to the ATP-binding cassette (ABC) transporter family, and zinT, which encodes a periplasmic zinc-binding protein. The expression of znuABC and zinT was inducible when cells were grown in medium containing a metal chelator (EDTA), and this induction was shown to be specific for zinc depletion. The expression of znuABC was reduced in response to increased zinc in a dose-dependent manner, and zinT had a less pronounced but similar pattern of zinc-regulated expression. The inactivation of zur led to constitutively high expression of znuABC and zinT. In addition, a zur mutant had an increased total zinc content compared to the WT NTL4 strain, whereas the inactivation of zinT caused a reduction in the total zinc content. The zinT gene is shown to play a dominant role and to be more important than znuA and znuB for A. tumefaciens survival under zinc deprivation. ZinT can function even when ZnuABC is inactivated. However, mutations in zur, znuA, znuB or zinT did not affect the virulence of A. tumefaciens.

scholarly journals The Zinc-Responsive Regulator Zur Controls a Zinc Uptake System and Some Ribosomal Proteins in Streptomyces coelicolor A3(2)

2007 ◽  
Vol 189 (11) ◽  
pp. 4070-4077 ◽  
Author(s):  
Jung-Ho Shin ◽  
So-Young Oh ◽  
Soon-Jong Kim ◽  
Jung-Hye Roe
Keyword(s):  
Ribosomal Proteins ◽  
Streptomyces Coelicolor ◽  
Regulatory System ◽  
Repeat Sequence ◽  
Zinc Uptake ◽  
Zinc Homeostasis ◽  
Transport Systems ◽  
Binding Motif ◽  
Uptake System ◽  
Zinc Depletion

ABSTRACT In various bacteria, Zur, a zinc-specific regulator of the Fur family, regulates genes for zinc transport systems to maintain zinc homeostasis. It has also been suggested that Zur controls zinc mobilization by regulating some ribosomal proteins. The antibiotic-producing soil bacterium Streptomyces coelicolor contains four genes for Fur family regulators, and one (named zur) is located downstream of the znuACB operon encoding a putative zinc uptake transporter. We found that zinc specifically repressed the level of znuA transcripts and that this level was derepressed in a Δzur mutant. Purified Zur existing as homodimers bound to the znuA promoter region in the presence of zinc, confirming the role of Zur as a zinc-responsive repressor. We analyzed transcripts for paralogous forms of ribosomal proteins L31 (RpmE1 and RpmE2) and L33 (RpmG2 and RpmG3) for their dependence on Zur and found that RpmE2 and RpmG2 with no zinc-binding motif of conserved cysteines (C's) were negatively regulated by Zur. C-negative RpmG3 and C-positive RpmE1 were not regulated by Zur. Instead, they were regulated by the sigma factor σR as predicted from their promoter sequences. The rpmE1 and rpmG3 genes were partially induced by EDTA in a manner dependent on σR, suggesting that zinc depletion may stimulate the σR regulatory system. This finding reflects a link between thiol-oxidizing stress and zinc depletion. We determined the Zur-binding sites within znuA and rpmG2 promoter regions by footprinting analyses and identified a consensus inverted repeat sequence (TGaaAatgatTttCA, where uppercase letters represent the nucleotides common to all sites analyzed). This sequence closely matches that for mycobacterial Zur and allows the prediction of more genes in the Zur regulon.

scholarly journals Coordinated Zinc Homeostasis Is Essential for the Wild-Type Virulence of Brucella abortus

2015 ◽  
Vol 197 (9) ◽  
pp. 1582-1591 ◽  
Author(s):  
Lauren M. Sheehan ◽  
James A. Budnick ◽  
R. Martin Roop ◽  
Clayton C. Caswell
Keyword(s):  
Mouse Model ◽  
Brucella Abortus ◽  
Zinc Uptake ◽  
Zinc Homeostasis ◽  
Zinc Toxicity ◽  
Uptake System ◽  
Bacterial Cells ◽  
Gene Encoding ◽  
Content Type ◽  
Genes Encoding

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 ofBrucella abortus; however, the capacity ofBrucellastrains 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 ofznuABC. Moreover, the MerR-type regulator, ZntR, controls the expression of the gene encoding the Zn exporter ZntA by binding directly to its promoter. Deletion ofzurorzntRalone did not result in increased zinc toxicity in the corresponding mutants; however, deletion ofzntAled 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 ofzntRresulted in significant attenuation ofB. abortusin a mouse model of chronic infection, and subsequent experiments revealed that overexpression ofzntAin thezntRmutant is the molecular basis for its decreased virulence.IMPORTANCEThe importance of zinc uptake forBrucellapathogenesis 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 inBrucella 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 ofBrucellavirulence in a mouse model. Overall, this study advances our understanding of the essential role of zinc in the pathogenesis of intracellular bacteria.

scholarly journals A link between zinc uptake, bile salts, and a capsule required for virulence of a mastitis-associated extraintestinal pathogenic Escherichia coli strain

2020 ◽  
Author(s):  
Michael A. Olson ◽  
Aleksander Grimsrud ◽  
Amanda C. Richards ◽  
Matthew A. Mulvey ◽  
Eric Wilson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bile Salts ◽  
Bloodstream Infections ◽  
Mouse Mammary Gland ◽  
Coli Strain ◽  
Zinc Uptake ◽  
Zinc Homeostasis ◽  
Growth Delay ◽  
Capsule Production

ABSTRACTExtraintestinal pathogenic Escherichia coli (ExPEC) are major causes of urinary and bloodstream infections. ExPEC reservoirs are not completely understood. Some mastitis-associated E. coli (MAEC) strains carry genes associated with ExPEC virulence, including metal scavenging, immune avoidance, and host attachment functions. In this study, we investigated the role of the high-affinity zinc uptake (znuABC) system in the MAEC strain M12. Elimination of znuABC moderately decreased fitness during mouse mammary gland infections. The ΔznuABC mutant strain exhibited an unexpected growth delay in the presence of bile salts, which was alleviated by the addition of excess zinc. We isolated ΔznuABC mutant suppressor mutants with improved growth of in bile salts, several of which no longer produced the K96 capsule made by strain M12. Addition of bile salts also reduced capsule production by strain M12 and ExPEC strain CP9, suggesting that capsule synthesis may be detrimental when bile salts are present. To better understand the role of the capsule, we compared the virulence of mastitis strain M12 with its unencapsulated ΔkpsCS mutant in two models of ExPEC disease. The wild type strain successfully colonized mouse bladders and kidneys and was highly virulent in intraperitoneal infections. Conversely, the ΔkpsCS mutant was unable to colonize kidneys and was unable to cause sepsis. These results demonstrate that some MAEC may be capable of causing human ExPEC illness. Virulence of strain M12 in these infections is dependent on its capsule. However, capsule may interfere with zinc homeostasis in the presence of bile salts while in the digestive tract.

scholarly journals Think zinc: Role of zinc poisoning in the intraphagosomal killing of bacteria by the amoeba Dictyostelium

2018 ◽  
Author(s):  
Caroline Barisch ◽  
Vera Kalinina ◽  
Louise H. Lefrançois ◽  
Joddy Appiah ◽  
Thierry Soldati
Keyword(s):  
Pathogenic Bacteria ◽  
Spatial Dynamics ◽  
Zinc Homeostasis ◽  
Particle Uptake ◽  
Metal Poisoning ◽  
Summary Statement ◽  
Soil Amoeba ◽  
The Impact ◽  
Role Of Zn

AbstractProfessional phagocytes have developed an extensive repertoire of autonomous immunity strategies to ensure killing of bacteria. Besides phagosome acidification and the generation of reactive oxygen species, deprivation of nutrients and the lumenal accumulation of toxic metals are essential to kill ingested bacteria or inhibit growth of intracellular pathogens. We use the soil amoeba Dictyostelium discoideum, a professional phagocyte that digests bacteria for nutritional purposes, to decipher the role of zinc poisoning during phagocytosis of non-pathogenic bacteria and visualize the temporal and spatial dynamics of compartmentalized, free zinc using fluorescent probes. Immediately after particle uptake, zinc is delivered to phagosomes by fusion with “zincosomes” of endosomal origin, but also by the action of one or more zinc transporters. We localize the four Dictyostelium ZnT transporters to endosomes, the contractile vacuole and the Golgi apparatus, and study the impact of znt knockouts on zinc homeostasis. Finally, we show that zinc is delivered into the lumen of Mycobacterium smegmatis-containing vacuoles, and that Escherichia coli deficient in the zinc efflux P1B-type ATPase ZntA is killed faster than wild type bacteria.Summary statementMetal poisoning is one of the bactericidal strategies of macrophages. Here, we describe the dynamics of free Zn and the role of Zn transporters during phagocytosis in Dictyostelium.

scholarly journals A Truncated Galectin-3 Isolated from Skin Mucus of Atlantic Salmon Salmo salar Binds to and Modulates the Proteome of the Gram-Negative Bacteria Moritella viscosa

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 102 ◽  
Author(s):  
Deepti Manjari Patel ◽  
Yoichiro Kitani ◽  
Kjetil Korsnes ◽  
Martin Haugmo Iversen ◽  
Monica Fengsrud Brinchmann
Keyword(s):  
Atlantic Salmon ◽  
Ribosomal Proteins ◽  
Pathogenic Bacteria ◽  
Short Form ◽  
Immune Defense ◽  
Spectrometric Analysis ◽  
Skin Mucus ◽  
Gram Negative ◽  
Isolation And Characterization ◽  
Galectin 3

The mucus of fish skin plays a vital role in innate immune defense. Some mucus proteins have the potential to incapacitate pathogens and/or inhibit their passage through the skin. In this study the aim was to isolate and characterize galectin(s), β-galactosides binding proteins, present in skin mucus. A novel short form of galectin-3 was isolated from Atlantic salmon skin mucus by α-lactose agarose based affinity chromatography followed by Sephadex G-15 gel filtration. Mass spectrometric analysis showed that the isolated protein was the C-terminal half of galectin-3 (galectin-3C). Galectin-3C showed calcium independent and lactose inhabitable hemagglutination, and agglutinated the Gram-negative pathogenic bacteria Moritella viscosa. Galectin-3 mRNA was highly expressed in skin and gill, followed by muscle, hindgut, spleen, stomach, foregut, head kidney, and liver. Moritella viscosa incubated with galectin-3C had a modified proteome. Proteins with changed abundance included multidrug transporter and three ribosomal proteins L7/12, S2, and S13. Overall, this study shows the isolation and characterization of a novel galectin-3 short form involved in pathogen recognition and modulation, and hence in immune defense of Atlantic salmon.

scholarly journals Control of Francisella tularensis Virulence at Gene Level: Network of Transcription Factors

2020 ◽  
Vol 8 (10) ◽  
pp. 1622
Author(s):  
Petra Spidlova ◽  
Pavla Stojkova ◽  
Anders Sjöstedt ◽  
Jiri Stulik
Keyword(s):  
Transcription Factors ◽  
Francisella Tularensis ◽  
Pathogenic Bacteria ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Experimental Studies ◽  
Initial Step ◽  
Research Area ◽  
Comprehensive Overview ◽  
Complex Process

Regulation of gene transcription is the initial step in the complex process that controls gene expression within bacteria. Transcriptional control involves the joint effort of RNA polymerases and numerous other regulatory factors. Whether global or local, positive or negative, regulators play an essential role in the bacterial cell. For instance, some regulators specifically modify the transcription of virulence genes, thereby being indispensable to pathogenic bacteria. Here, we provide a comprehensive overview of important transcription factors and DNA-binding proteins described for the virulent bacterium Francisella tularensis, the causative agent of tularemia. This is an unexplored research area, and the poorly described networks of transcription factors merit additional experimental studies to help elucidate the molecular mechanisms of pathogenesis in this bacterium, and how they contribute to disease.

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