A Single Nucleotide Change Affects Fur-Dependent Regulation of sodB in H. pylori

Carpenter, Beth M.; Gancz, Hanan; Gonzalez-Nieves, Reyda P.; West, Abby L.; Whitmire, Jeannette M.; Michel, Sarah L. J.; Merrell, D. Scott

doi:10.1371/journal.pone.0005369

Cited by 35 publications

(61 citation statements)

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“…RNase protection assays (RPAs) were performed essentially as previously described (10,25,26). In brief, liquid cultures of wild-type (WT) and ⌬fur G27 were grown to exponential phase, and one half of each culture was removed for RNA isolation.…”

Section: Methodsmentioning

confidence: 99%

“…H. pylori responds and adapts to gastric stressors by altering gene expression through the use of transcriptional regulators. One such regulator, the ferric uptake regulator (Fur), is utilized to maintain iron homeostasis (4-6) but also to respond to pH (7)(8)(9), nitrosative, and oxidative stressors (10)(11)(12). Given the paucity of transcriptional regulators found in H. pylori compared to other bacterial organisms (13), it is perhaps not surprising that through the course of evolution, H. pylori Fur has taken on a more global role in gene regulation beyond iron uptake and storage.…”

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confidence: 99%

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Identification and Characterization of Novel Helicobacter pylori apo-Fur-Regulated Target Genes

et al. 2013

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cIn Helicobacter pylori, the ferric uptake regulator (Fur) has evolved additional regulatory functions not seen in other bacteria; it can repress and activate different groups of genes in both its iron-bound and apo forms. Because little is understood about the process of apo-Fur repression and because only two apo-Fur-repressed genes (pfr and sodB) have previously been identified, we sought to expand our understanding of this type of regulation. Utilizing published genomic studies, we selected three potential new apo-Fur-regulated gene targets: serB, hydA, and the cytochrome c 553 gene. Transcriptional analyses confirmed Fur-dependent repression of these genes in the absence of iron, as well as derepression in the absence of Fur. Binding studies showed that apo-Fur directly interacted with the suspected hydA and cytochrome c 553 promoters but not that of serB, which was subsequently shown to be cotranscribed with pfr; apo-Fur-dependent regulation occurred at the pfr promoter. Alignments of apo-regulated promoter regions revealed a conserved, 6-bp consensus sequence (AAATGA). DNase I footprinting showed that this sequence lies within the protected regions of the pfr and hydA promoters. Moreover, mutation of the sequence in the pfr promoter abrogated Fur binding and DNase protection. Likewise, fluorescence anisotropy studies and binding studies with mutated consensus sequences showed that the sequence was important for apo-Fur binding to the pfr promoter. Together these studies expand the known apo-Fur regulon in H. pylori and characterize the first reported apo-Fur box sequence.

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Section: Methodsmentioning

confidence: 99%

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Identification and Characterization of Novel Helicobacter pylori apo-Fur-Regulated Target Genes

et al. 2013

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“…For example, although Fur and NikR are classically thought of as metallo-regulators, in H. pylori, they also play an important role in acid acclimation (10,26). Furthermore, Fur has been shown to be important for adaptation to oxidative, nitrosative, and osmotic stress (27)(28)(29). Thus, further study of the intricate interaction between each of these regulatory factors may provide increased information about the adaptation process of H. pylori.…”

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Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation

et al. 2016

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Helicobacter pylori must be able to rapidly respond to fluctuating conditions within the stomach. Despite this need for constant adaptation, H. pylori encodes few regulatory proteins. Of the identified regulators, the ferric uptake regulator (Fur), the nickel response regulator (NikR), and the two-component acid response system (ArsRS) are each paramount to the success of this pathogen. While numerous studies have individually examined these regulatory proteins, little is known about their combined effect. Therefore, we constructed a series of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS. A growth curve analysis revealed minor variation in growth kinetics across the strains; these were most pronounced in the triple mutant and in strains lacking ArsS. Visual analysis showed that strains lacking ArsS formed large aggregates and a biofilm-like matrix at the air-liquid interface. Biofilm quantification using crystal violet assays and visualization via scanning electron microscopy (SEM) showed that all strains lacking ArsS or containing a nonphosphorylatable form of ArsR (ArsR-D52N mutant) formed significantly more biofilm than the wild-type strain. Molecular characterization of biofilm formation showed that strains containing mutations in the ArsRS pathway displayed increased levels of cell aggregation and adherence, both of which are key to biofilm development. Furthermore, SEM analysis revealed prevalent coccoid cells and extracellular matrix formation in the ArsR-D52N, ⌬nikR ⌬arsS, and ⌬fur ⌬nikR ⌬arsS mutant strains, suggesting that these strains may have an exacerbated stress response that further contributes to biofilm formation. Thus, H. pylori ArsRS has a previously unrecognized role in biofilm formation. IMPORTANCEDespite a paucity of regulatory proteins, adaptation is key to the survival of H. pylori within the stomach. While prior studies have focused on individual regulatory proteins, such as Fur, NikR, and ArsRS, few studies have examined the combined effect of these factors. Analysis of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS revealed a previously unrecognized role for the acid-responsive two-component system ArsRS in biofilm formation.

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“…In both instances, apo-Fur binds specifically to promoters under metal-free conditions. In the case of sodB, a single nucleotide substitution in the Fur box results in altered apo-Fur regulation (78). Promoter sequence comparison of these two genes failed to highlight a putative binding sequence, and homology to the proposed Fe 2ϩ -Fur consensus is not evident (79,161).…”

Section: Vol 75 2011 Variations In Mechanisms Of Epsilonproteobactementioning

confidence: 97%

“…In H. pylori, the upstream region of these genes appears to contain a putative Fur box (based on a consensus proposed by Merrell et al [416]), but direct activation by Fur has not yet been demonstrated for H. pylori. apo-Fur has been shown to regulate expression of pfr and sodB (54,78,160,161). Other genes putatively repressed by apo-Fur include serB (encoding a phosphoserine phosphatase), genes involved in energy metabolism, such as hydA and hydB, and several genes with unknown or hypothetical function (160).…”

Section: Vol 75 2011 Variations In Mechanisms Of Epsilonproteobactementioning

confidence: 99%

Change Is Good: Variations in Common Biological Mechanisms in the Epsilonproteobacterial GeneraCampylobacterandHelicobacter

Gilbreath

Cody

Merrell

et al. 2011

Microbiol Mol Biol Rev

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SUMMARY Microbial evolution and subsequent species diversification enable bacterial organisms to perform common biological processes by a variety of means. The epsilonproteobacteria are a diverse class of prokaryotes that thrive in diverse habitats. Many of these environmental niches are labeled as extreme, whereas other niches include various sites within human, animal, and insect hosts. Some epsilonproteobacteria, such as Campylobacter jejuni and Helicobacter pylori , are common pathogens of humans that inhabit specific regions of the gastrointestinal tract. As such, the biological processes of pathogenic Campylobacter and Helicobacter spp. are often modeled after those of common enteric pathogens such as Salmonella spp. and Escherichia coli . While many exquisite biological mechanisms involving biochemical processes, genetic regulatory pathways, and pathogenesis of disease have been elucidated from studies of Salmonella spp. and E. coli , these paradigms often do not apply to the same processes in the epsilonproteobacteria. Instead, these bacteria often display extensive variation in common biological mechanisms relative to those of other prototypical bacteria. In this review, five biological processes of commonly studied model bacterial species are compared to those of the epsilonproteobacteria C. jejuni and H. pylori . Distinct differences in the processes of flagellar biosynthesis, DNA uptake and recombination, iron homeostasis, interaction with epithelial cells, and protein glycosylation are highlighted. Collectively, these studies support a broader view of the vast repertoire of biological mechanisms employed by bacteria and suggest that future studies of the epsilonproteobacteria will continue to provide novel and interesting information regarding prokaryotic cellular biology.

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A Single Nucleotide Change Affects Fur-Dependent Regulation of sodB in H. pylori

Cited by 35 publications

References 37 publications

Identification and Characterization of Novel Helicobacter pylori apo-Fur-Regulated Target Genes

Identification and Characterization of Novel Helicobacter pylori apo-Fur-Regulated Target Genes

Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation

Change Is Good: Variations in Common Biological Mechanisms in the Epsilonproteobacterial GeneraCampylobacterandHelicobacter

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