scholarly journals Role of autoregulation and relative synthesis of operon partners in alternative sigma factor networks

2015 ◽  
Author(s):  
Jatin Narula ◽  
Abhinav Tiwari ◽  
Oleg A. Igoshin
Keyword(s):  
Bacillus Subtilis ◽  
Stress Response ◽  
Negative Feedback ◽  
Sigma Factor ◽  
Critical Role ◽  
Sigma Factors ◽  
Alternative Sigma Factor ◽  
Negative Feedback Regulation ◽  
Alternative Sigma Factors

SummaryDespite the central role of alternative sigma factors in bacterial stress response and virulence their regulation remains incompletely understood. Here we investigate one of the best-studied examples of alternative sigma factors: the σBnetwork that controls the general stress response ofBacillus subtilisto uncover widely relevant general design principles that describe the structure-function relationship of alternative sigma factor regulatory networks. We show that the relative stoichiometry of the synthesis rates of σB, its anti-sigma factor RsbW and the anti-anti-sigma factor RsbV plays a critical role in shaping the network behavior by forcing the σBnetwork to function as an ultrasensitive negative feedback loop. We further demonstrate how this negative feedback regulation insulates alternative sigma factor activity from competition with the housekeeping sigma factor for RNA polymerase and allows multiple stress sigma factors to function simultaneously with little competitive interference.Major Subject Areas:Computational and systems biology, Microbiology & Infectious diseaseResearch Organism:Bacillus subtilis

scholarly journals Transcriptional Regulation and Mechanism of SigN (ZpdN), a pBS32-Encoded Sigma Factor in Bacillus subtilis

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Aisha T. Burton ◽  
Aaron DeLoughery ◽  
Gene-Wei Li ◽  
Daniel B. Kearns
Keyword(s):  
Dna Damage ◽  
Bacillus Subtilis ◽  
Sigma Factor ◽  
Consensus Sequence ◽  
Sigma Factors ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Content Type ◽  
Alternative Sigma Factors ◽  
Bona Fide

ABSTRACT Laboratory strains of Bacillus subtilis encode many alternative sigma factors, each dedicated to expressing a unique regulon such as those involved in stress resistance, sporulation, and motility. The ancestral strain of B. subtilis also encodes an additional sigma factor homolog, ZpdN, not found in lab strains due to being encoded on the large, low-copy-number plasmid pBS32, which was lost during domestication. DNA damage triggers pBS32 hyperreplication and cell death in a manner that depends on ZpdN, but how ZpdN mediates these effects is unknown. Here, we show that ZpdN is a bona fide sigma factor that can direct RNA polymerase to transcribe ZpdN-dependent genes, and we rename ZpdN SigN accordingly. Rend-seq (end-enriched transcriptome sequencing) analysis was used to determine the SigN regulon on pBS32, and the 5′ ends of transcripts were used to predict the SigN consensus sequence. Finally, we characterize the regulation of SigN itself and show that it is transcribed by at least three promoters: PsigN1, a strong SigA-dependent LexA-repressed promoter; PsigN2, a weak SigA-dependent constitutive promoter; and PsigN3, a SigN-dependent promoter. Thus, in response to DNA damage SigN is derepressed and then experiences positive feedback. How cells die in a pBS32-dependent manner remains unknown, but we predict that death is the product of expressing one or more genes in the SigN regulon. IMPORTANCE Sigma factors are utilized by bacteria to control and regulate gene expression. Some sigma factors are activated during times of stress to ensure the survival of the bacterium. Here, we report the presence of a sigma factor that is encoded on a plasmid that leads to cellular death after DNA damage.

scholarly journals Translational activation by an alternative sigma factor in Bacillus subtilis

2021 ◽  
Author(s):  
Dylan M. McCormick ◽  
Jean-Benoît Lalanne ◽  
Tammy C. T. Lan ◽  
Silvi Rouskin ◽  
Gene-Wei Li
Keyword(s):  
Bacillus Subtilis ◽  
Sigma Factor ◽  
Rna Folding ◽  
Secondary Structures ◽  
Sigma Factors ◽  
Bacterial Transcription ◽  
Regulate Protein ◽  
Transcriptional Induction

ABSTRACTSigma factors are an important class of bacterial transcription factors that lend specificity to RNA polymerases by binding to distinct promoter elements for genes in their regulons. Here we show that activation of the general stress sigma factor, σB, in Bacillus subtilis paradoxically leads to dramatic induction of translation for a subset of its regulon genes. These genes are translationally repressed when transcribed by the housekeeping sigma factor, σA, owing to extended RNA secondary structures as determined in vivo using DMS-MaPseq. Transcription from σB-dependent promoters liberates the secondary structures and activates translation, leading to dual induction. Translation efficiencies between σB- and σA-dependent RNA isoforms can vary by up to 100-fold, which in multiple cases exceeds the magnitude of transcriptional induction. These results highlight the role of long-range RNA folding in modulating translation and demonstrate that a transcription factor can regulate protein synthesis beyond its effects on transcript levels.

scholarly journals The Alternative Sigma Factor SigB Is Required for the Pathogenicity of Bacillus thuringiensis

2020 ◽  
Vol 202 (21) ◽  
Author(s):  
Stéphanie Henry ◽  
Didier Lereclus ◽  
Leyla Slamti
Keyword(s):  
Life Cycle ◽  
Stress Response ◽  
Bacillus Thuringiensis ◽  
Sigma Factor ◽  
Oral Route ◽  
Alternative Sigma Factor ◽  
Gram Positive ◽  
Content Type ◽  
General Stress Response

ABSTRACT To adapt to changing and potentially hostile environments, bacteria can activate the transcription of genes under the control of alternative sigma factors, such as SigB, a master regulator of the general stress response in several Gram-positive species. Bacillus thuringiensis is a Gram-positive spore-forming invertebrate pathogen whose life cycle includes a variety of environments, including plants and the insect hemocoel or gut. Here, we assessed the role of SigB during the infectious cycle of B. thuringiensis in a Galleria mellonella insect model. We used a fluorescent reporter coupled to flow cytometry and showed that SigB was activated in vivo. We also showed that the pathogenicity of the ΔsigB mutant was severely affected when inoculated via the oral route, suggesting that SigB is critical for B. thuringiensis adaptation to the gut environment of the insect. We could not detect an effect of the sigB deletion on the survival of the bacteria or on their sporulation efficiency in the cadavers. However, the gene encoding the pleiotropic regulator Spo0A was upregulated in the ΔsigB mutant cells during the infectious process. IMPORTANCE Pathogenic bacteria often need to transition between different ecosystems, and their ability to cope with such variations is critical for their survival. Several Gram-positive species have developed an adaptive response mediated by the general stress response alternative sigma factor SigB. In order to understand the ecophysiological role of this regulator in Bacillus thuringiensis, an entomopathogenic bacterium widely used as a biopesticide, we sought to examine the fate of a ΔsigB mutant during its life cycle in the natural setting of an insect larva. This allowed us, in particular, to show that SigB was activated during infection and that it was required for the pathogenicity of B. thuringiensis via the oral route of infection.

scholarly journals The Staphylococcus aureus Alternative Sigma Factor ςB Controls the Environmental Stress Response but Not Starvation Survival or Pathogenicity in a Mouse Abscess Model

1998 ◽  
Vol 180 (23) ◽  
pp. 6082-6089 ◽  
Author(s):  
Pan F. Chan ◽  
Simon J. Foster ◽  
Eileen Ingham ◽  
Mark O. Clements
Keyword(s):  
Staphylococcus Aureus ◽  
Stress Response ◽  
Environmental Stress ◽  
Sigma Factor ◽  
Osmotic Shock ◽  
Alternative Sigma Factor ◽  
Dependent Manner ◽  
Virulence Determinant ◽  
Starvation Survival

ABSTRACT The role of ςB, an alternative sigma factor ofStaphylococcus aureus, has been characterized in response to environmental stress, starvation-survival and recovery, and pathogenicity. ςB was mainly expressed during the stationary phase of growth and was repressed by 1 M sodium chloride. AsigB insertionally inactivated mutant was created. In stress resistance studies, ςB was shown to be involved in recovery from heat shock at 54°C and in acid and hydrogen peroxide resistance but not in resistance to ethanol or osmotic shock. Interestingly, S. aureus acquired increased acid resistance when preincubated at a sublethal pH 4 prior to exposure to a lethal pH 2. This acid-adaptive response resulting in tolerance was mediated viasigB. However, ςB was not vital for the starvation-survival or recovery mechanisms. ςB does not have a major role in the expression of the global regulator of virulence determinant biosynthesis, staphylococcal accessory regulator (sarA), the production of a number of representative virulence factors, and pathogenicity in a mouse subcutaneous abscess model. However, SarA upregulates sigB expression in a growth-phase-dependent manner. Thus, ςB expression is linked to the processes controlling virulence determinant production. The role of ςB as a major regulator of the stress response, but not of starvation-survival, is discussed.

scholarly journals Pivotal role of the Francisella tularensis heat-shock sigma factor RpoH

Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2560-2572 ◽  
Author(s):  
Nathalie Grall ◽  
Jonathan Livny ◽  
Matthew Waldor ◽  
Monique Barel ◽  
Alain Charbit ◽  
...  
Keyword(s):  
Heat Shock ◽  
Francisella Tularensis ◽  
Sigma Factor ◽  
Bacterial Species ◽  
Bioinformatic Analysis ◽  
Alternative Sigma Factor ◽  
Heat Stress Response ◽  
Alternative Sigma Factors ◽  
Genes Encoding

Francisella tularensis is a highly infectious pathogen that infects animals and humans to cause the disease tularemia. The primary targets of this bacterium are macrophages, in which it replicates in the cytoplasm after escaping the initial phagosomal compartment. The ability to replicate within macrophages relies on the tightly regulated expression of a series of genes. One of the most commonly used means of coordinating the regulation of multiple genes in bacteria consists of the association of dedicated alternative sigma factors with the core of the RNA polymerase (RNAP). In silico analysis of the F. tularensis LVS genome led us to identify, in addition to the genes encoding the RNAP core (comprising the α1, α2, β, β′ and ω subunits), one gene (designated rpoD) encoding the major sigma factor σ 70, and a unique gene (FTL_0851) encoding a putative alternative sigma factor homologue of the σ 32 heat-shock family (designated rpoH). Hence, F. tularensis represents one of the minority of bacterial species that possess only one or no alternative sigma factor in addition to the main factor σ 70. In the present work, we show that FTL_0851 encodes a genuine σ 32 factor. Transcriptomic analyses of the F. tularensis LVS heat-stress response allowed the identification of a series of orthologues of known heat-shock genes (including those for Hsp40, GroEL, GroES, DnaK, DnaJ, GrpE, ClpB and ClpP) and a number of genes implicated in Francisella virulence. A bioinformatic analysis was used to identify genes preceded by a putative σ 32-binding site, revealing both similarities to and differences from RpoH-mediated gene expression in Escherichia coli. Our results suggest that RpoH is an essential protein of F. tularensis, and positively regulates a subset of genes involved in the heat-shock response.

scholarly journals An Amino Acid Substitution in RNA Polymerase That Inhibits the Utilization of an Alternative Sigma Factor

2017 ◽  
Vol 199 (14) ◽  
Author(s):  
Anna F. Wang Erickson ◽  
Padraig Deighan ◽  
Cinthia P. Garcia ◽  
Robert O. J. Weinzierl ◽  
Ann Hochschild ◽  
...  
Keyword(s):  
Amino Acid ◽  
Rna Polymerase ◽  
Amino Acid Substitution ◽  
Sigma Factor ◽  
Coiled Coil ◽  
Sigma Factors ◽  
Alternative Sigma Factor ◽  
Content Type ◽  
Alternative Sigma Factors ◽  
Σ Factor

ABSTRACT Sigma (σ) factors direct gene transcription by binding to and determining the promoter recognition specificity of RNA polymerase (RNAP) in bacteria. Genes transcribed under the control of alternative sigma factors allow cells to respond to stress and undergo developmental processes, such as sporulation in Bacillus subtilis, in which gene expression is controlled by a cascade of alternative sigma factors. Binding of sigma factors to RNA polymerase depends on the coiled-coil (or clamp helices) motif of the β′ subunit. We have identified an amino acid substitution (L257P) in the coiled coil that markedly inhibits the function of σH, the earliest-acting alternative sigma factor in the sporulation cascade. Cells with this mutant RNAP exhibited an early and severe block in sporulation but not in growth. The mutant was strongly impaired in σH-directed gene expression but not in the activity of the stress-response sigma factor σB. Pulldown experiments showed that the mutant RNAP was defective in associating with σH but could still associate with σA and σB. The differential effects of the L257P substitution on sigma factor binding to RNAP are likely due to a conformational change in the β′ coiled coil that is specifically detrimental for interaction with σH. This is the first example, to our knowledge, of an amino acid substitution in RNAP that exhibits a strong differential effect on a particular alternative sigma factor. IMPORTANCE In bacteria, all transcription is mediated by a single multisubunit RNA polymerase (RNAP) enzyme. However, promoter-specific transcription initiation necessitates that RNAP associates with a σ factor. Bacteria contain a primary σ factor that directs transcription of housekeeping genes and alternative σ factors that direct transcription in response to environmental or developmental cues. We identified an amino acid substitution (L257P) in the B. subtilis β′ subunit whereby RNAPL257P associates with some σ factors (σA and σB) and enables vegetative cell growth but is defective in utilization of σH and is consequently blocked for sporulation. To our knowledge, this is the first identification of an amino acid substitution within the core enzyme that affects utilization of a specific sigma factor.

scholarly journals Growth Phase-Dependent Regulation of the Extracytoplasmic Stress Factor, σE, by Guanosine 3′,5′-Bispyrophosphate (ppGpp)

2006 ◽  
Vol 188 (13) ◽  
pp. 4627-4634 ◽  
Author(s):  
Alessandra Costanzo ◽  
Sarah E. Ades
Keyword(s):  
Escherichia Coli ◽  
Stationary Phase ◽  
Growth Phase ◽  
Sigma Factor ◽  
Sigma Factors ◽  
Alternative Sigma Factor ◽  
Dependent Manner ◽  
Alternative Sigma Factors ◽  
Promoter Recognition ◽  
Sigma Subunit

ABSTRACT The sigma subunit of procaryotic RNA polymerases is responsible for specific promoter recognition and transcription initiation. In addition to the major sigma factor, σ70, in Escherichia coli, which directs most of the transcription in the cell, bacteria possess multiple, alternative sigma factors that direct RNA polymerase to distinct sets of promoters in response to environmental signals. By activating an alternative sigma factor, gene expression can be rapidly reprogrammed to meet the needs of the cell as the environment changes. Sigma factors are subject to multiple levels of regulation that control their levels and activities. The alternative sigma factor σE in Escherichia coli is induced in response to extracytoplasmic stress. Here we demonstrate that σE can also respond to signals other than extracytoplasmic stress. σE activity increases in a growth phase-dependent manner as a culture enters stationary phase. The signaling pathway that activates σE during entry into stationary phase is dependent upon the alarmone guanosine 3′,5′-bispyrophosphate (ppGpp) and is distinct from the pathway that signals extracytoplasmic stress. ppGpp is the first cytoplasmic factor shown to control σE activity, demonstrating that σE can respond to internal signals as well as signals originating in the cell envelope. ppGpp is a general signal of starvation stress and is also required for activation of the σS and σ54 alternative sigma factors upon entry into stationary phase, suggesting that this is a key mechanism by which alternative sigma factors can be activated in concert to provide a coordinated response to nutritional stress.

scholarly journals Mitochondrien unter Stress: Die Rolle der Präsequenzprotease MPP

BIOspektrum ◽  
2021 ◽  
Vol 27 (4) ◽  
pp. 390-393
Author(s):  
F.-Nora Vögtle
Keyword(s):  
Stress Response ◽  
Cellular Stress ◽  
Critical Role ◽  
Mitochondrial Protein ◽  
Nuclear Genome ◽  
Cellular Stress Response ◽  
Mitochondrial Proteins ◽  
Protein Biogenesis ◽  
Cellular Integrity

AbstractThe majority of mitochondrial proteins are encoded in the nuclear genome, so that the nearly entire proteome is assembled by post-translational preprotein import from the cytosol. Proteomic imbalances are sensed and induce cellular stress response pathways to restore proteostasis. Here, the mitochondrial presequence protease MPP serves as example to illustrate the critical role of mitochondrial protein biogenesis and proteostasis on cellular integrity.

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