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Bacterial Regulatory Proteins 2.0
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Bacterial Regulatory Proteins 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 10368

Special Issue Editor

Dr. Jan Kormanec

E-Mail Website
Guest Editor
Institute of Molecular Biology, Slovak Academy of Sciences, 845 51 Bratislava, Slovakia
Interests: streptomyces genetics; biologically active secondary metabolites; regulation of antibiotics biosynthesis; sigma factors of RNA polymerase, gene expression
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sigma factors are important regulatory subunits of RNA polymerase that confer promoter specificity to the RNA polymerase catalytic core enzyme. Upon association with core RNA polymerase, sigma factors allow the recognition of specific promoters, thus directing the expression of a specific set of genes (so-called regulon of the corresponding sigma factor). Most bacteria contain an essential primary sigma factor directing expression of “house-keeping” genes, and one or more alternative sigma factors responsive to various stimuli necessary to survive adverse stress conditions (including immune responses during host infection with pathogenic bacteria) and to differentiate bacterial cells. The complexity of cell life corresponds to a number of sigma factors. For example, the obligate intracellular pathogen Mycoplasma pneumoniae has only a single primary sigma factor, and the other obligate pathogen Chlamydia trachomatis has three sigma factors, but the saprophytic differentiating unicellular Bacillus subtilis contains 18 sigma factors and the hyphal differentiating Streptomyces coelicolor contains even 65 different sigma factors. Sigma factors dissociate from the RNA polymerase holoenzyme following the transcription initiation process. Therefore, a free core RNA polymerase pool is available to competitively bind various sigma factors, thereby reprogramming gene expression for the actual bacterial needs. Due to this competitive step of regulation, the most important step in almost all sigma factors is the regulation of their levels, which takes place at the transcriptional, translational, and post-translational level.

One common mechanism of the posttranslational regulation is the reversible interaction with their cognate negative regulators, anti-sigma factors, which sequester them from their interaction with the core RNA polymerase. After a variety of signals, this complex is released very rapidly, making the sigma factor free for their association with the core RNA polymerase to direct transcription of a set of cognate genes. This allows a very quick response to various adverse stress conditions. In addition to sigma factors, many other regulatory proteins contribute to the regulation of gene expression at the transcriptional level. Negative regulator (repressors) generally bind to promoters and block the access of the RNA polymerase holoenzyme to activate transcription. Positive regulators usually bind in the upstream regions of promoters, associate with the RNA polymerase holoenzyme, and allow activation of transcription of the cognate promoters.

This Special Issue will address the role of sigma factors of RNA polymerase and other specific regulatory proteins in various bacterial processes, including stress response, bacterial pathogenesis, and morphological cell differentiation. Research articles and reviews focusing on this topic are welcome.

Dr. Jan Kormanec
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sigma factor
  • regulatory proteins
  • repressors
  • activators
  • pathogenesis
  • cell differentiation
  • regulation
  • gene expression
  • RNA polymerase
  • stress response

Related Special Issue

Published Papers (6 papers)

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Research

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14 pages, 2770 KiB  
Article
The Sigma Factor AsbI Is Required for the Expression of Acinetobactin Siderophore Transport Genes in Aeromonas salmonicida
by Diego Rey-Varela, Miguel Balado and Manuel L. Lemos
Int. J. Mol. Sci. 2023, 24(11), 9672; https://doi.org/10.3390/ijms24119672 - 02 Jun 2023
Viewed by 932
Abstract
Aeromonas salmonicida subsp. salmonicida (A. salmonicida), a Gram-negative bacterium causing furunculosis in fish, produces the siderophores acinetobactin and amonabactins in order to extract iron from its hosts. While the synthesis and transport of both systems is well understood, the regulation pathways [...] Read more.
Aeromonas salmonicida subsp. salmonicida (A. salmonicida), a Gram-negative bacterium causing furunculosis in fish, produces the siderophores acinetobactin and amonabactins in order to extract iron from its hosts. While the synthesis and transport of both systems is well understood, the regulation pathways and conditions necessary for the production of each one of these siderophores are not clear. The acinetobactin gene cluster carries a gene (asbI) encoding a putative sigma factor belonging to group 4 σ factors, or, the ExtraCytoplasmic Function (ECF) group. By generating a null asbI mutant, we demonstrate that AsbI is a key regulator that controls acinetobactin acquisition in A. salmonicida, since it directly regulates the expression of the outer membrane transporter gene and other genes necessary for Fe-acinetobactin transport. Furthermore, AsbI regulatory functions are interconnected with other iron-dependent regulators, such as the Fur protein, as well as with other sigma factors in a complex regulatory network. Full article
(This article belongs to the Special Issue Bacterial Regulatory Proteins 2.0)
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20 pages, 4115 KiB  
Article
Site-2 Protease Slr1821 Regulates Carbon/Nitrogen Homeostasis during Ammonium Stress Acclimation in Cyanobacterium Synechocystis sp. PCC 6803
by Shiqi Lin, Shiliang Li, Tong Ouyang and Gu Chen
Int. J. Mol. Sci. 2023, 24(7), 6606; https://doi.org/10.3390/ijms24076606 - 01 Apr 2023
Cited by 1 | Viewed by 1492
Abstract
Excess ammonium imposes toxicity and stress response in cyanobacteria. How cyanobacteria acclimate to NH4+ stress is so far poorly understood. Here, Synechocystis sp. PCC6803 S2P homolog Slr1821 was identified as the essential regulator through physiological characterization and transcriptomic analysis of its [...] Read more.
Excess ammonium imposes toxicity and stress response in cyanobacteria. How cyanobacteria acclimate to NH4+ stress is so far poorly understood. Here, Synechocystis sp. PCC6803 S2P homolog Slr1821 was identified as the essential regulator through physiological characterization and transcriptomic analysis of its knockout mutant. The proper expression of 60% and 67% of the NH4+ activated and repressed genes, respectively, were actually Slr1821-dependent since they were abolished or reversed in ∆slr1821. Synechocystis 6803 suppressed nitrogen uptake and assimilation, ammonium integration and mobilization of other nitrogen sources upon NH4+ stress. Opposite regulation on genes for assimilation of nitrogen and carbon, such as repression of nitrogen regulatory protein PII, PII interactive protein PirC and activation of carbon acquisition regulator RcbR, demonstrated that Synechocystis 6803 coordinated regulation to maintain carbon/nitrogen homeostasis under increasing nitrogen, while functional Slr1821 was indispensable for most of this coordinated regulation. Additionally, slr1821 knockout disrupted the proper response of regulators and transporters in the ammonium-specific stimulon, and resulted in defective photosynthesis as well as compromised translational and transcriptional machinery. These results provide new insight into the coordinated regulation of nutritional fluctuation and the functional characterization of S2Ps. They also provide new targets for bioengineering cyanobacteria in bioremediation and improving ammonium tolerance in crop plants. Full article
(This article belongs to the Special Issue Bacterial Regulatory Proteins 2.0)
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21 pages, 4950 KiB  
Article
Insight into the Global Negative Regulation of Iron Scavenger 7-HT Biosynthesis by the SigW/RsiW System in Pseudomonas donghuensis HYS
by Shiyu Teng, Tingting Wu, Donghao Gao, Siyi Wu, Yaqian Xiao, Yan Long and Zhixiong Xie
Int. J. Mol. Sci. 2023, 24(2), 1184; https://doi.org/10.3390/ijms24021184 - 07 Jan 2023
Viewed by 1652
Abstract
7-Hydroxytropolone (7-HT) is a unique iron scavenger synthesized by Pseudomonas donghuensis HYS that has various biological activities in addition to functioning as a siderophore. P. donghuensis HYS is more pathogenic than P. aeruginosa toward Caenorhabditis elegans, an observation that is closely linked [...] Read more.
7-Hydroxytropolone (7-HT) is a unique iron scavenger synthesized by Pseudomonas donghuensis HYS that has various biological activities in addition to functioning as a siderophore. P. donghuensis HYS is more pathogenic than P. aeruginosa toward Caenorhabditis elegans, an observation that is closely linked to the biosynthesis of 7-HT. The nonfluorescent siderophore (nfs) gene cluster is responsible for the orderly biosynthesis of 7-HT and represents a competitive advantage that contributes to the increased survival of P. donghuensis HYS; however, the regulatory mechanisms of 7-HT biosynthesis remain unclear. This study is the first to propose that the ECF σ factor has a regulatory effect on 7-HT biosynthesis. In total, 20 ECF σ factors were identified through genome-wide scanning, and their responses to extracellular ferrous ions were characterized. We found that SigW was both significantly upregulated under high-iron conditions and repressed by an adjacent anti-σ factor. RNA-Seq results suggest that the SigW/RsiW system is involved in iron metabolism and 7-HT biosynthesis. Combined with the siderophore phenotype, we also found that SigW could inhibit siderophore synthesis, and this inhibition can be relieved by RsiW. EMSA assays proved that SigW, when highly expressed, can directly bind to the promoter region of five operons of the nfs cluster to inhibit the transcription of the corresponding genes and consequently suppress 7-HT biosynthesis. In addition, SigW not only directly negatively regulates structural genes related to 7-HT synthesis but also inhibits the transcription of regulatory proteins, including of the Gac/Rsm cascade system. Taken together, our results highlight that the biosynthesis of 7-HT is negatively regulated by SigW and that the SigW/RsiW system is involved in mechanisms for the regulation of iron homeostasis in P. donghuensis HYS. As a result of this work, we identified a novel mechanism for the global negative regulation of 7-HT biosynthesis, complementing our understanding of the function of ECF σ factors in Pseudomonas. Full article
(This article belongs to the Special Issue Bacterial Regulatory Proteins 2.0)
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35 pages, 5618 KiB  
Article
Comparative Proteomic Analysis of Transcriptional and Regulatory Proteins Abundances in S. lividans and S. coelicolor Suggests a Link between Various Stresses and Antibiotic Production
by Lejeune Clara, Cornu David, Sago Laila, Redeker Virginie and Virolle Marie-Joelle
Int. J. Mol. Sci. 2022, 23(23), 14792; https://doi.org/10.3390/ijms232314792 - 26 Nov 2022
Cited by 5 | Viewed by 1506
Abstract
Streptomyces coelicolor and Streptomyces lividans constitute model strains to study the regulation of antibiotics biosynthesis in Streptomyces species since these closely related strains possess the same pathways directing the biosynthesis of various antibiotics but only S. coelicolor produces them. To get a better [...] Read more.
Streptomyces coelicolor and Streptomyces lividans constitute model strains to study the regulation of antibiotics biosynthesis in Streptomyces species since these closely related strains possess the same pathways directing the biosynthesis of various antibiotics but only S. coelicolor produces them. To get a better understanding of the origin of the contrasted abilities of these strains to produce bioactive specialized metabolites, these strains were grown in conditions of phosphate limitation or proficiency and a comparative analysis of their transcriptional/regulatory proteins was carried out. The abundance of the vast majority of the 355 proteins detected greatly differed between these two strains and responded differently to phosphate availability. This study confirmed, consistently with previous studies, that S. coelicolor suffers from nitrogen stress. This stress likely triggers the degradation of the nitrogen-rich peptidoglycan cell wall in order to recycle nitrogen present in its constituents, resulting in cell wall stress. When an altered cell wall is unable to fulfill its osmo-protective function, the bacteria also suffer from osmotic stress. This study thus revealed that these three stresses are intimately linked in S. coelicolor. The aggravation of these stresses leading to an increase of antibiotic biosynthesis, the connection between these stresses, and antibiotic production are discussed. Full article
(This article belongs to the Special Issue Bacterial Regulatory Proteins 2.0)
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18 pages, 3588 KiB  
Article
Impact of a Novel PagR-like Transcriptional Regulator on Cereulide Toxin Synthesis in Emetic Bacillus cereus
by Eva Maria Kalbhenn, Markus Kranzler, Agnieszka Gacek-Matthews, Gregor Grass, Timo D. Stark, Elrike Frenzel and Monika Ehling-Schulz
Int. J. Mol. Sci. 2022, 23(19), 11479; https://doi.org/10.3390/ijms231911479 - 29 Sep 2022
Cited by 4 | Viewed by 1762
Abstract
The emetic type of foodborne disease caused by Bacillus cereus is produced by the small peptide toxin cereulide. The genetic locus encoding the Ces nonribosomal peptide synthetase (CesNRPS) multienzyme machinery is located on a 270 kb megaplasmid, designated pCER270, which shares its backbone [...] Read more.
The emetic type of foodborne disease caused by Bacillus cereus is produced by the small peptide toxin cereulide. The genetic locus encoding the Ces nonribosomal peptide synthetase (CesNRPS) multienzyme machinery is located on a 270 kb megaplasmid, designated pCER270, which shares its backbone with the Bacillus anthracis toxin plasmid pXO1. Although the ces genes are plasmid-borne, the chromosomally encoded pleiotropic transcriptional factors CodY and AbrB are key players in the control of ces transcription. Since these proteins only repress cereulide synthesis during earlier growth phases, other factors must be involved in the strict control of ces expression and its embedment in the bacterial life cycle. In silico genome analysis revealed that pCER270 carries a putative ArsR/SmtB family transcription factor showing high homology to PagR from B. anthracis. As PagR plays a crucial role in the regulation of the protective antigen gene pagA, which forms part of anthrax toxin, we used a gene-inactivation approach, combined with electrophoretic mobility shift assays and a bacterial two-hybrid system for dissecting the role of the PagR homologue PagRBc in the regulation of cereulide synthesis. Our results highlight that the plasmid-encoded transcriptional regulator PagRBc plays an important role in the complex and multilayered process of cereulide synthesis. Full article
(This article belongs to the Special Issue Bacterial Regulatory Proteins 2.0)
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Review

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23 pages, 1585 KiB  
Review
Insights into the Orchestration of Gene Transcription Regulators in Helicobacter pylori
by Andrea Vannini, Davide Roncarati, Federico D’Agostino, Federico Antoniciello and Vincenzo Scarlato
Int. J. Mol. Sci. 2022, 23(22), 13688; https://doi.org/10.3390/ijms232213688 - 08 Nov 2022
Cited by 5 | Viewed by 2413
Abstract
Bacterial pathogens employ a general strategy to overcome host defenses by coordinating the virulence gene expression using dedicated regulatory systems that could raise intricate networks. During the last twenty years, many studies of Helicobacter pylori, a human pathogen responsible for various stomach [...] Read more.
Bacterial pathogens employ a general strategy to overcome host defenses by coordinating the virulence gene expression using dedicated regulatory systems that could raise intricate networks. During the last twenty years, many studies of Helicobacter pylori, a human pathogen responsible for various stomach diseases, have mainly focused on elucidating the mechanisms and functions of virulence factors. In parallel, numerous studies have focused on the molecular mechanisms that regulate gene transcription to attempt to understand the physiological changes of the bacterium during infection and adaptation to the environmental conditions it encounters. The number of regulatory proteins deduced from the genome sequence analyses responsible for the correct orchestration of gene transcription appears limited to 14 regulators and three sigma factors. Furthermore, evidence is accumulating for new and complex circuits regulating gene transcription and H. pylori virulence. Here, we focus on the molecular mechanisms used by H. pylori to control gene transcription as a function of the principal environmental changes. Full article
(This article belongs to the Special Issue Bacterial Regulatory Proteins 2.0)
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