The Blue-Light Receptor YtvA Acts in the Environmental Stress Signaling Pathway of Bacillus subtilis

ABSTRACT The general stress response of the bacterium Bacillus subtilis is regulated by a partner-switching mechanism in which serine and threonine phosphorylation controls protein interactions in the stress-signaling pathway. The environmental branch of this pathway contains a family of five paralogous proteins that function as negative regulators. Here we present genetic evidence that a sixth paralog, YtvA, acts as a positive regulator in the same environmental signaling branch. We also present biochemical evidence that YtvA and at least three of the negative regulators can be isolated from cell extracts in a large environmental signaling complex. YtvA differs from these associated negative regulators by its flavin mononucleotide (FMN)-containing light-oxygen-voltage domain. Others have shown that this domain has the photochemistry expected for a blue-light sensor, with the covalent linkage of the FMN chromophore to cysteine 62 composing a critical part of the photocycle. Consistent with the view that light intensity modifies the output of the environmental signaling pathway, we found that cysteine 62 is required for YtvA to exert its positive regulatory role in the absence of other stress. Transcriptional analysis of the ytvA structural gene indicated that it provides the entry point for at least one additional environmental input, mediated by the Spx global regulator of disulfide stress. These results support a model in which the large signaling complex serves to integrate multiple environmental signals in order to modulate the general stress response.

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Modeling the functioning of YtvA in the general stress response in Bacillus subtilis

Molecular BioSystems ◽

10.1039/c3mb70124g ◽

2013 ◽

Vol 9 (9) ◽

pp. 2331 ◽

Cited By ~ 10

Author(s):

Jeroen B. van der Steen ◽

Yusuke Nakasone ◽

Johnny Hendriks ◽

Klaas J. Hellingwerf

Keyword(s):

Bacillus Subtilis ◽

Stress Response ◽

General Stress Response ◽

General Stress

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General Stress Response in Bacillus subtilis and Related Gram-Positive Bacteria

Bacterial Stress Responses, Second Edition ◽

10.1128/9781555816841.ch17 ◽

2014 ◽

pp. 301-318 ◽

Cited By ~ 14

Author(s):

Chester W. Price

Keyword(s):

Bacillus Subtilis ◽

Stress Response ◽

Gram Positive ◽

General Stress Response ◽

Gram Positive Bacteria ◽

General Stress

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Exposure of Bacillus subtilis to Low Pressure (5 Kilopascals) Induces Several Global Regulons, Including Those Involved in the SigB-Mediated General Stress Response

Applied and Environmental Microbiology ◽

10.1128/aem.00885-14 ◽

2014 ◽

Vol 80 (16) ◽

pp. 4788-4794 ◽

Cited By ~ 12

Author(s):

Samantha M. Waters ◽

José A. Robles-Martínez ◽

Wayne L. Nicholson

Keyword(s):

Bacillus Subtilis ◽

Stress Response ◽

High Pressures ◽

Low Pressure ◽

Bacterial Cells ◽

Content Type ◽

General Stress Response ◽

Cellular Processes ◽

General Stress ◽

Microbial Responses

ABSTRACTStudies of how microorganisms respond to pressure have been limited mostly to the extreme high pressures of the deep sea (i.e., the piezosphere). In contrast, despite the fact that the growth of most bacteria is inhibited at pressures below ∼2.5 kPa, little is known of microbial responses to low pressure (LP). To study the global LP response, we performed transcription microarrays onBacillus subtiliscells grown under normal atmospheric pressure (∼101 kPa) and a nearly inhibitory LP (5 kPa), equivalent to the pressure found at an altitude of ∼20 km. Microarray analysis revealed altered levels of 363 transcripts belonging to several global regulons (AbrB, CcpA, CodY, Fur, IolR, ResD, Rok, SigH, Spo0A). Notably, the highest number of upregulated genes, 86, belonged to the SigB-mediated general stress response (GSR) regulon. Upregulation of the GSR by LP was confirmed by monitoring the expression of the SigB-dependentctc-lacZreporter fusion. Measuring transcriptome changes resulting from exposure of bacterial cells to LP reveals insights into cellular processes that may respond to LP exposure.

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Oxidative Stress Signaling Pathway of Heme Regulated eIF2α Kinase in mitigating the Severity of β-Thalassemia

Blood ◽

10.1182/blood.v112.11.127.127 ◽

2008 ◽

Vol 112 (11) ◽

pp. 127-127 ◽

Cited By ~ 3

Author(s):

Rajasekhar NVS Suragani ◽

Sijin Liu ◽

Wanting Zhao ◽

Jane-Jane Chen

Keyword(s):

Oxidative Stress ◽

Protein Synthesis ◽

Stress Response ◽

Signaling Pathway ◽

Fetal Liver ◽

Stress Signaling ◽

Erythroid Precursors ◽

Inhibition Of Protein Synthesis ◽

And Oxidative Stress ◽

Stress Signaling Pathway

Abstract Maturation of erythroid precursors requires active synthesis of hemoglobin which consists of two pairs of α- and β-globin subunits with each monomer bound to a heme moiety. Heme Regulated Inhibitor (HRI) is the only eIF2αkinase responsible for the balanced synthesis of heme and globin at translational level in erythroid cells. Activation of HRI in heme deficiency leads to phosphorylation of the α-subunit of eukaryotic initiation factor (eIF2α) and inhibition of protein synthesis. HRI is also activated by denatured proteins and oxidative stress. In addition to general inhibition of protein synthesis, phosphorylation of eIF2α (eIF2αP) also leads to the induction of a stress signaling pathway. Activating transcription factor 4 (Atf4) mRNA is preferentially translated amidst global inhibition of protein synthesis. Atf4 activates transcription of stress response proteins, Chop (CCAAT/enhancer binding protein homologous protein-10) and the non-enzymatic cofactor of eIF2α phosphatase (PP1A) Gadd34. These stress response proteins help cells in mitigating the stress. While the role of HRI in translational regulation of non-nucleated reticulocytes is well established, the HRIdependent Atf4 stress signaling pathway of nucleated erythroid precursors is unknown. Sodium arsenite toxicity was used as a model system of oxidative stress to elucidate the HRI signaling pathway in Hri +/+ and −/− E14.5 mouse fetal liver erythroid precursors. In HRI deficiency, erythroid precursors were more sensitive to arsenite toxicity with decreased cell viability and increased apoptosis, by caspase 3 executed intrinsic apoptotic pathway. HRI was activated by autophosphorylation as early as 15 minutes following arsenite treatment. In addition to increased eIF2αP, there was induction of Atf4, Chop and Gadd34 in Hri+/+ fetal liver cells. Importantly, in Hri−/− cells neither the phosphorylation of eIF2α nor the expression of Atf4, Chop and Gadd34 was increased upon arsenite treatment. In addition, we also observed HRI dependent induction of Heme Oxygenase 1 (HO-1) that plays a pivotal role in adaptation to oxidative stress. These results demonstrate that HRI induces a signaling pathway for adaptive gene expression to protect the nucleated erythroid precursors from apoptosis upon oxidative stress. Iron overload, accumulation of unpaired α-globin and oxidative stress are well documented in β-thalassemia. Recently, HRI was discovered to be necessary for the survival of β-thalassemic mice. β-thalassemic mice lacking one copy of HRI (Hri+/− Hbb−/−) also manifest a more severe syndrome of the disease. We have investigated the activation of eIF2αP/Atf4 signaling pathway in Hri+/−Hbb−/− β-thalassemic erythroid cells using eIF2αP phosphatase (Gadd34) inhibitor salubrinal. Treatment of reticulocytes from Hri+/−Hbb−/− mice with salubrinal increased eIF2αP and resulted in inhibition of newly synthesized globin protein synthesis. The decreased globin protein synthesis also resulted in decreased aggregation of the unpaired α-globins. Furthermore, treatment of salubrinal in nucleated fetal liver erythroblasts also increased Chop expression and decreased apoptosis. Thus, activation of the eIF2αP/Atf4 pathway by small chemicals might be a novel pharmaceutical approach to decrease proteotoxicity and apoptosis for the treatment of β-thalassemia.

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Blue Light Activates the σB-Dependent Stress Response of Bacillus subtilis via YtvA

Journal of Bacteriology ◽

10.1128/jb.00716-06 ◽

2006 ◽

Vol 188 (17) ◽

pp. 6411-6414 ◽

Cited By ~ 119

Author(s):

Marcela Ávila-Pérez ◽

Klaas J. Hellingwerf ◽

Remco Kort

Keyword(s):

Bacillus Subtilis ◽

Stress Response ◽

Blue Light ◽

Promoter Activity ◽

Red Light ◽

Light Response ◽

Soil Bacterium ◽

Light Illumination ◽

Present Evidence ◽

General Stress Response

ABSTRACT Here we present evidence for a physiologically relevant light response mediated by the LOV domain-containing protein YtvA in the soil bacterium Bacillus subtilis. The loss and overproduction of YtvA abolish and enhance, respectively, the increase in σB-controlled ctc promoter activity at moderate light intensities. These effects were absent in the dark and in red light but present under blue-light illumination. Thus, activation of the general stress response in B. subtilis is modulated by blue light.

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Global Transcriptional Response of Bacillus subtilis to Heat Shock

Journal of Bacteriology ◽

10.1128/jb.183.24.7318-7328.2001 ◽

2001 ◽

Vol 183 (24) ◽

pp. 7318-7328 ◽

Cited By ~ 187

Author(s):

John D. Helmann ◽

Ming Fang Winston Wu ◽

Phil A. Kobel ◽

Francisco-Javier Gamo ◽

Michael Wilson ◽

...

Keyword(s):

Bacillus Subtilis ◽

Stress Response ◽

Heat Shock ◽

Dna Sequences ◽

Stress Responses ◽

Transcriptional Response ◽

Transcriptional Responses ◽

General Stress Response ◽

General Stress ◽

Induced Genes

ABSTRACT In response to heat stress, Bacillus subtilisactivates the transcription of well over 100 different genes. Many of these genes are members of a general stress response regulon controlled by the secondary sigma factor, ςB, while others are under control of the HrcA or CtsR heat shock regulators. We have used DNA microarrays to monitor the global transcriptional response to heat shock. We find strong induction of known ςB-dependent genes with a characteristic rapid induction followed by a return to near prestimulus levels. The HrcA and CtsR regulons are also induced, but with somewhat slower kinetics. Analysis of DNA sequences proximal to newly identified heat-induced genes leads us to propose ∼70 additional members of the ςB regulon. We have also identified numerous heat-induced genes that are not members of known heat shock regulons. Notably, we observe very strong induction of arginine biosynthesis and transport operons. Induction of several genes was confirmed by quantitative reverse transcriptase PCR. In addition, the transcriptional responses measured by microarray hybridization compare favorably with the numerous previous studies of heat shock in this organism. Since many different conditions elicit both specific and general stress responses, knowledge of the heat-induced general stress response reported here will be helpful for interpreting future microarray studies of other stress responses.

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