Dataset Information

Beyond Repression: ArsR Functions as a Global Activator of Metabolic and Redox Responses in Escherichia Coli

ABSTRACT: The arsenic-responsive repressor, ArsR, has long been understood as a canonical regulator of the arsRBC operon, which confers resistance to arsenic stress. However, recent studies suggest a broader regulatory scope for ArsR. Here, we investigated the proteomic landscape of Escherichia coli strains with and without ArsR to elucidate ArsR as an activator in both non-stressing and arsenic-stressing conditions. Using mass spectrometry-based shotgun proteomics and statistical analyses, we characterized the differential abundance of proteins across AW3110 (ΔarsRBC), AW3110 complemented with arsR, and wild-type K-12 strains under control and arsenite-stressed conditions. Our study shows ArsR influences proteomic networks beyond the ars operon, integrating metabolic and redox responses crucial for cellular adaptation and survival. This suggests that ArsR has a significant role in gut microbiome metabolomic profiles in response to arsenite. Proteins involved in alanine, lactaldehyde, arginine, thioredoxin, and proline pathways were significantly elevated in strains where ArsR was detected, both with and without arsenite. We identified proteins exhibiting an “ArsR-dependent” activation pattern, highlighting ArsR’s potential role in redox balance and energy metabolism. These findings challenge the classical view of ArsR as a re-pressor and position it as a pleiotropic regulator including broad activation.

INSTRUMENT(S):

ORGANISM(S): Escherichia Coli

SUBMITTER: Monika Tokmina-Lukaszewska

LAB HEAD: Brian Bothner

PROVIDER: PXD071635 | Pride | 2026-02-02

REPOSITORIES: Pride

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			Action	DRS
	BothnerB_020724_Lysate_01.raw	Raw
	BothnerB_020724_Lysate_02.raw	Raw
	BothnerB_020724_Lysate_03.raw	Raw
	BothnerB_020724_Lysate_04.raw	Raw
	BothnerB_020724_Lysate_05.raw	Raw

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Publications

Beyond Repression: ArsR Functions as a Global Activator of Metabolic and Redox Responses in <i>Escherichia coli</i>.

Sather Brett B Larson James J Hutt Vater Kian K Westrum Jade J McDermott Timothy R TR Bothner Brian B

Proteomes 20260104 1

<h4>Background</h4>The arsenic-responsive repressor, ArsR, has long been understood as a canonical regulator of the <i>arsRBC</i> operon, which confers resistance to arsenic stress. However, recent studies suggest a broader regulatory scope for ArsR. Here, we investigated the proteomic landscape of <i>Escherichia coli</i> strains with and without ArsR to elucidate ArsR as an activator in both non-stressing and arsenic-stressing conditions.<h4>Methods</h4>Using mass-spectrometry-based shotgun pro ...[more]

PMID: 41562852

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Project description:Arsenic is an ubiquitous contaminant and a toxic metalloid which presents two main redox states in nature: arsenite [AsIII] and arsenate [AsV]. Arsenic resistance in Synechocystis sp. strain PCC 6803 is mediated by the arsBHC operon and two additional arsenate reductases encoded by the arsI1 and arsI2 genes. Here we describe the genome-wide responses in response to the presence of arsenate and arsenite in wild type and in mutants in the arsenic resistance system. Both forms of arsenic produced similar responses in the wild type strain including induction of several stress related genes and repression of energy generation processes. The responses observed in the arsB mutant strain were similar to the wild type in short term but were maintained in time while they were only transient in the wild type strain. In contrast, the responses observed in a strain lacking all arsenate reductases (the SARS12 strain) were somewhat different and included lower induction of genes involved in metal homeostasis and Fe-S cluster biogenesis. These results suggest that these two processes are targeted by arsenite in the wild type strain. Finally, analysis of the arsR mutant strain revealed that ArsR seems to only control 5 genes in the genome. Furthermore, over-expression of ArsB conferred hypersentivity to nickel, copper and cadmium in an arsR mutant strain. Analysis of genome-wide gene expression patterns in response to arsenic in WT and mutants involved in arsenic detoxification in the cyanobacterium Synechocystis sp PCC 6803. Cells treated with arsenate or arsenite for 1h. Details: WT cells were treated with 1 mM arsenite for 1 h and its expression profile compared to untreated cells (grown in BG11C media). The effects of arsenate were analyzed in the same way but using a modified BG11C media that constains 15% of the normal phosphate concentration (BG11C low phosphate). A reduction in the phosphate concentration in the media is essential to detect grow inhibition after arsenate addition. In the same way that for arsenite cells were treated with 50 mM arsenate for 1 h and their expression profile was compared to untreated cells. Expression profiles of mutant strains lacking arsB gene (SARSB strain; this strain is hypersensitive to arsenite because it lacks the arsenite exporter) or arsR gene (SARSR strain; this strain expresses the arsBHC constitutively) in control conditions and in response to arsenite addition were also analyzed. In addition the expression profiles of a mutant lacking arsenate reductases (SARS12 strain that has interrupted arsC, arsI1 and arsI2 genes; this strain is hypersensitive to arsenate) were analyzed in both control conditions and after addition of 50 mM arsenate.

Project description:Arsenic (As) exposure is a significant worldwide environmental health concern. Low dose, chronic arsenic exposure has been associated with higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. While arsenic-induced biological changes play a role in disease pathology, little is known about the dynamic cellular changes due to arsenic exposure and withdrawal. In these studies, we seek to understand the molecular mechanisms behind the biological changes induced by chronic low doses of arsenic exposure. We used a comprehensive approach involving chromatin structural studies and mRNA microarray analyses to determine how chromatin structure and gene expression patterns change in response to chronic low dose arsenic exposure and its subsequent withdrawal. Our results show that cells exposed to low doses of sodium arsenite have distinct temporal and coordinated chromatin, gene expression and miRNA changes that are consistent with differentiation and activation of multiple biochemical pathways. Most of these temporal patterns in gene expression are reversed when arsenic was withdrawn. However, some of the gene expression patterns remained altered, plausibly as a result of an adaptive response by these cells. Additionally, these gene expression patterns correlated with changes in chromatin structure, further solidifying the role of chromatin structure in gene regulatory changes due to arsenite exposure. Lastly, we show that arsenite exposure influences gene regulation both at the transcription initiation as well as at the splicing level. Thus our results suggest that general patterns of alternative splicing, as well as expression of particular gene regulators, can be indicative of arsenite-induced cell transformation. A total of eight (8) samples with two biological replicates under four separate conditions: wild-type treated with deionized H2O for 36 days (NT); chronic low-dose arsenic exposure of 1 uM of sodium arsenite (iAs-T) for 36 days; chronic arsenic exposure of 1 uM of sodium arsenite for 26 days followed by removal of sodium arsenite for 10 days, measured at day 36 (iAs-Rev); and chronic arsenic exposure of 1 uM of sodium arsenite for 26 days, followed by removal of sodium arsenite exposure for 10 days, followed by 1 uM of chronic sodium arsenite exposure for 10 days (measured at day 46) (iAs-Rev-T).

Project description:Talemi2014 - Arsenic toxicity and detoxification mechanisms in yeast The model implements arsenite (AsIII) transport regulation, its distribution within main cellular AsIII pools and detoxification. The intracellular As pools considered are free AsIII (AsIIIin), protein-bound AsIII (AsIIIprot), glutathione conjugated AsIII (AsGS3) and vacuolar sequestered AsIII (vAsGS3). This model is described in the article: Mathematical modelling of arsenic transport, distribution and detoxification processes in yeast. Talemi SR, Jacobson T, Garla V, Navarrete C, Wagner A, Tamás MJ, Schaber J. Mol. Microbiol. 2014 Jun; 92(6): 1343-1356 Abstract: Arsenic has a dual role as causative and curative agent of human disease. Therefore, there is considerable interest in elucidating arsenic toxicity and detoxification mechanisms. By an ensemble modelling approach, we identified a best parsimonious mathematical model which recapitulates and predicts intracellular arsenic dynamics for different conditions and mutants, thereby providing novel insights into arsenic toxicity and detoxification mechanisms in yeast, which could partly be confirmed experimentally by dedicated experiments. Specifically, our analyses suggest that: (i) arsenic is mainly protein-bound during short-term (acute) exposure, whereas glutathione-conjugated arsenic dominates during long-term (chronic) exposure, (ii) arsenic is not stably retained, but can leave the vacuole via an export mechanism, and (iii) Fps1 is controlled by Hog1-dependent and Hog1-independent mechanisms during arsenite stress. Our results challenge glutathione depletion as a key mechanism for arsenic toxicity and instead suggest that (iv) increased glutathione biosynthesis protects the proteome against the damaging effects of arsenic and that (v) widespread protein inactivation contributes to the toxicity of this metalloid. Our work in yeast may prove useful to elucidate similar mechanisms in higher eukaryotes and have implications for the use of arsenic in medical therapy. This model is hosted on BioModels Database and identified by: BIOMD0000000547. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Beyond Repression: ArsR Functions as a Global Activator of Metabolic and Redox Responses in Escherichia Coli

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Beyond Repression: ArsR Functions as a Global Activator of Metabolic and Redox Responses in <i>Escherichia coli</i>.

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Dataset Information

Beyond Repression: ArsR Functions as a Global Activator of Metabolic and Redox Responses in Escherichia Coli

Dataset's files

Publications

Beyond Repression: ArsR Functions as a Global Activator of Metabolic and Redox Responses in &lt;i&gt;Escherichia coli&lt;/i&gt;.

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OmicsDI is part of the ELIXIR infrastructure

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Beyond Repression: ArsR Functions as a Global Activator of Metabolic and Redox Responses in <i>Escherichia coli</i>.