International Journal of Molecular Sciences

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5 pages, 213 KiB

Open AccessEditorial

Bacterial Regulatory Proteins

by Jan Kormanec

Int. J. Mol. Sci. 2022, 23(12), 6854; https://doi.org/10.3390/ijms23126854 - 20 Jun 2022

Cited by 1 | Viewed by 1420

Abstract

The regulation of gene expression in bacteria occurs predominantly at the level of transcription, which is controlled by RNA polymerase [...] Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

Research

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27 pages, 3147 KiB

Open AccessArticle

Staphylococcal saoABC Operon Codes for a DNA-Binding Protein SaoC Implicated in the Response to Nutrient Deficit

by Michal Bukowski, Maja Kosecka-Strojek, Anna Madry, Rafal Zagorski-Przybylo, Tomasz Zadlo, Katarzyna Gawron and Benedykt Wladyka

Int. J. Mol. Sci. 2022, 23(12), 6443; https://doi.org/10.3390/ijms23126443 - 09 Jun 2022

Cited by 1 | Viewed by 1858

Abstract

Whilst a large number of regulatory mechanisms for gene expression have been characterised to date, transcription regulation in bacteria still remains an open subject. In clinically relevant and opportunistic pathogens, such as Staphylococcus aureus, transcription regulation is of great importance for host-pathogen [...] Read more.

Whilst a large number of regulatory mechanisms for gene expression have been characterised to date, transcription regulation in bacteria still remains an open subject. In clinically relevant and opportunistic pathogens, such as Staphylococcus aureus, transcription regulation is of great importance for host-pathogen interactions. In our study we investigated an operon, exclusive to staphylococci, that we name saoABC. We showed that SaoC binds to a conserved sequence motif present upstream of the saoC gene, which likely provides a negative feedback loop. We have also demonstrated that S. aureus ΔsaoB and ΔsaoC mutants display altered growth dynamics in non-optimal media; ΔsaoC exhibits decreased intracellular survival in human dermal fibroblasts, whereas ΔsaoB produces an elevated number of persisters, which is also elicited by inducible production of SaoC in ΔsaoBΔsaoC double mutant. Moreover, we have observed changes in the expression of saoABC operon genes during either depletion of the preferential carbon or the amino acid source as well as during acidification. Comparative RNA-Seq of the wild type and ΔsaoC mutant demonstrated that SaoC influences transcription of genes involved in amino acid transport and metabolism, and notably of those coding for virulence factors. Our results suggest compellingly that saoABC operon codes for a DNA-binding protein SaoC, a novel staphylococcal transcription factor, and its antagonist SaoB. We linked SaoC to the response to nutrient deficiency, a stress that has a great impact on host-pathogen interactions. That impact manifests in SaoC influence on persister formation and survival during internalisation to host cells, as well as on the expression of genes of virulence factors that may potentially result in profound alternations in the pathogenic phenotype. Investigation of such novel regulatory mechanisms is crucial for our understanding of the dynamics of interactions between pathogenic bacteria and host cells, particularly in the case of clinically relevant, opportunistic pathogens such as Staphylococcus aureus. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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20 pages, 4890 KiB

Open AccessArticle

The SCO2102 Protein Harbouring a DnaA II Protein-Interaction Domain Is Essential for the SCO2103 Methylenetetrahydrofolate Reductase Positioning at Streptomyces Sporulating Hyphae, Enhancing DNA Replication during Sporulation

by Gemma Fernández-García, Nathaly González-Quiñónez, Beatriz Rioseras, Sergio Alonso-Fernández, Javier Fernández, Felipe Lombó and Ángel Manteca

Int. J. Mol. Sci. 2022, 23(9), 4984; https://doi.org/10.3390/ijms23094984 - 30 Apr 2022

Cited by 1 | Viewed by 1543

Abstract

Streptomyces DNA replication starts with the DnaA binding to the origin of replication. Differently to most bacteria, cytokinesis only occurs during sporulation. Cytokinesis is modulated by the divisome, an orderly succession of proteins initiated by FtsZ. Here, we characterised SCO2102, a protein harbouring [...] Read more.

Streptomyces DNA replication starts with the DnaA binding to the origin of replication. Differently to most bacteria, cytokinesis only occurs during sporulation. Cytokinesis is modulated by the divisome, an orderly succession of proteins initiated by FtsZ. Here, we characterised SCO2102, a protein harbouring a DnaA II protein–protein interaction domain highly conserved in Streptomyces. The ΔSCO2102 knockout shows highly delayed sporulation. SCO2102-mCherry frequently co-localises with FtsZ-eGFP during sporulation and greatly reduces FtsZ-eGFP Z-ladder formation, suggesting a role of SCO2102 in sporulation. SCO2102 localises up-stream of SCO2103, a methylenetetrahydrofolate reductase involved in methionine and dTMP synthesis. SCO2102/SCO2103 expression is highly regulated, involving two promoters and a conditional transcription terminator. The ΔSCO2103 knockout shows reduced DNA synthesis and a non-sporulating phenotype. SCO2102-mCherry co-localises with SCO2103-eGFP during sporulation, and SCO2102 is essential for the SCO2103 positioning at sporulating hyphae, since SCO2103-eGFP fluorescent spots are absent in the ΔSCO2102 knockout. We propose a model in which SCO2102 positions SCO2103 in sporulating hyphae, facilitating nucleotide biosynthesis for chromosomal replication. To the best of our knowledge, SCO2102 is the first protein harbouring a DnaA II domain specifically found during sporulation, whereas SCO2103 is the first methylenetetrahydrofolate reductase found to be essential for Streptomyces sporulation. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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20 pages, 1970 KiB

Open AccessArticle

The Transcription Factor SpoVG Is of Major Importance for Biofilm Formation of Staphylococcus epidermidis under In Vitro Conditions, but Dispensable for In Vivo Biofilm Formation

by Hannah Benthien, Beate Fresenborg, Linda Pätzold, Mohamed Ibrahem Elhawy, Sylvaine Huc-Brandt, Christoph Beisswenger, Gabriela Krasteva-Christ, Sören L. Becker, Virginie Molle, Johannes K. Knobloch and Markus Bischoff

Int. J. Mol. Sci. 2022, 23(6), 3255; https://doi.org/10.3390/ijms23063255 - 17 Mar 2022

Cited by 3 | Viewed by 2145

Abstract

Staphylococcus epidermidis is a common cause of device related infections on which pathogens form biofilms (i.e., multilayered cell populations embedded in an extracellular matrix). Here, we report that the transcription factor SpoVG is essential for the capacity of S. epidermidis to form such [...] Read more.

Staphylococcus epidermidis is a common cause of device related infections on which pathogens form biofilms (i.e., multilayered cell populations embedded in an extracellular matrix). Here, we report that the transcription factor SpoVG is essential for the capacity of S. epidermidis to form such biofilms on artificial surfaces under in vitro conditions. Inactivation of spoVG in the polysaccharide intercellular adhesin (PIA) producing S. epidermidis strain 1457 yielded a mutant that, unlike its parental strain, failed to produce a clear biofilm in a microtiter plate-based static biofilm assay. A decreased biofilm formation capacity was also observed when 1457 ΔspoVG cells were co-cultured with polyurethane-based peripheral venous catheter fragments under dynamic conditions, while the cis-complemented 1457 ΔspoVG::spoVG derivative formed biofilms comparable to the levels seen with the wild-type. Transcriptional studies demonstrated that the deletion of spoVG significantly altered the expression of the intercellular adhesion (ica) locus by upregulating the transcription of the ica operon repressor icaR and down-regulating the transcription of icaADBC. Electrophoretic mobility shift assays (EMSA) revealed an interaction between SpoVG and the icaA-icaR intergenic region, suggesting SpoVG to promote biofilm formation of S. epidermidis by modulating ica expression. However, when mice were challenged with the 1457 ΔspoVG mutant in a foreign body infection model, only marginal differences in biomasses produced on the infected catheter fragments between the mutant and the parental strain were observed. These findings suggest that SpoVG is critical for the PIA-dependent biofilm formation of S. epidermis under in vitro conditions, but is largely dispensable for biofilm formation of this skin commensal under in vivo conditions. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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21 pages, 3462 KiB

Open AccessArticle

A New Family of Transcriptional Regulators Activating Biosynthetic Gene Clusters for Secondary Metabolites

by Renata Novakova, Erik Mingyar, Lubomira Feckova, Dagmar Homerova, Dominika Csolleiova, Bronislava Rezuchova, Beatrica Sevcikova, Rachel Javorova and Jan Kormanec

Int. J. Mol. Sci. 2022, 23(5), 2455; https://doi.org/10.3390/ijms23052455 - 23 Feb 2022

Cited by 5 | Viewed by 1935

Abstract

We previously identified the aur1 biosynthetic gene cluster (BGC) in Streptomyceslavendulae subsp. lavendulae CCM 3239 (formerly Streptomycesaureofaciens CCM 3239), which is responsible for the production of the unusual angucycline-like antibiotic auricin. Auricin is produced in a narrow interval of the growth [...] Read more.

We previously identified the aur1 biosynthetic gene cluster (BGC) in Streptomyceslavendulae subsp. lavendulae CCM 3239 (formerly Streptomycesaureofaciens CCM 3239), which is responsible for the production of the unusual angucycline-like antibiotic auricin. Auricin is produced in a narrow interval of the growth phase after entering the stationary phase, after which it is degraded due to its instability at the high pH values reached after the production phase. The complex regulation of auricin BGC is responsible for this specific production by several regulators, including the key activator Aur1P, which belongs to the family of atypical response regulators. The aur1P gene forms an operon with the downstream aur1O gene, which encodes an unknown protein without any conserved domain. Homologous aur1O genes have been found in several BGCs, which are mainly responsible for the production of angucycline antibiotics. Deletion of the aur1O gene led to a dramatic reduction in auricin production. Transcription from the previously characterized Aur1P-dependent biosynthetic aur1Ap promoter was similarly reduced in the S. lavendulaeaur1O mutant strain. The aur1O-specific coactivation of the aur1Ap promoter was demonstrated in a heterologous system using a luciferase reporter gene. In addition, the interaction between Aur1O and Aur1P has been demonstrated by a bacterial two-hybrid system. These results suggest that Aur1O is a specific coactivator of this key auricin-specific positive regulator Aur1P. Bioinformatics analysis of Aur1O and its homologues in other BGCs revealed that they represent a new family of transcriptional coactivators involved in the regulation of secondary metabolite biosynthesis. However, they are divided into two distinct sequence-specific subclasses, each of which is likely to interact with a different family of positive regulators. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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15 pages, 3735 KiB

Open AccessArticle

GntR-like SCO3932 Protein Provides a Link between Actinomycete Integrative and Conjugative Elements and Secondary Metabolism

by Krzysztof J. Pawlik, Mateusz Zelkowski, Mateusz Biernacki, Katarzyna Litwinska, Pawel Jaworski and Magdalena Kotowska

Int. J. Mol. Sci. 2021, 22(21), 11867; https://doi.org/10.3390/ijms222111867 - 01 Nov 2021

Cited by 4 | Viewed by 1824

Abstract

Streptomyces bacteria produce a plethora of secondary metabolites including the majority of medically important antibiotics. The onset of secondary metabolism is correlated with morphological differentiation and controlled by a complex regulatory network involving numerous regulatory proteins. Control over these pathways at the molecular [...] Read more.

Streptomyces bacteria produce a plethora of secondary metabolites including the majority of medically important antibiotics. The onset of secondary metabolism is correlated with morphological differentiation and controlled by a complex regulatory network involving numerous regulatory proteins. Control over these pathways at the molecular level has a medical and industrial importance. Here we describe a GntR-like DNA binding transcription factor SCO3932, encoded within an actinomycete integrative and conjugative element, which is involved in the secondary metabolite biosynthesis regulation. Affinity chromatography, electrophoresis mobility shift assay, footprinting and chromatin immunoprecipitation experiments revealed, both in vitro and in vivo, SCO3932 binding capability to its own promoter region shared with the neighboring gene SCO3933, as well as promoters of polyketide metabolite genes, such as cpkD, a coelimycin biosynthetic gene, and actII-orf4—an activator of actinorhodin biosynthesis. Increased activity of SCO3932 target promoters, as a result of SCO3932 overproduction, indicates an activatory role of this protein in Streptomyces coelicolor A3(2) metabolite synthesis pathways. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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17 pages, 3695 KiB

Open AccessArticle

The Modulation of SCO2730/31 Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in Streptomycetes

by Nathaly González-Quiñónez, Ignacio Gutiérrez-Del-Río, Paula García-Cancela, Gemma Fernández-García, Sergio Alonso-Fernández, Paula Yagüe, Álvaro Pérez-Valero, María Montes-Bayón, Felipe Lombó and Ángel Manteca

Int. J. Mol. Sci. 2021, 22(18), 10143; https://doi.org/10.3390/ijms221810143 - 20 Sep 2021

Cited by 3 | Viewed by 1900

Abstract

Streptomycetes are important biotechnological bacteria that produce several clinically bioactive compounds. They have a complex development, including hyphae differentiation and sporulation. Cytosolic copper is a well-known modulator of differentiation and secondary metabolism. The interruption of the Streptomyces coelicolor SCO2730 (copper chaperone, SCO2730::Tn5062 mutant) [...] Read more.

Streptomycetes are important biotechnological bacteria that produce several clinically bioactive compounds. They have a complex development, including hyphae differentiation and sporulation. Cytosolic copper is a well-known modulator of differentiation and secondary metabolism. The interruption of the Streptomyces coelicolor SCO2730 (copper chaperone, SCO2730::Tn5062 mutant) blocks SCO2730 and reduces SCO2731 (P-type ATPase copper export) expressions, decreasing copper export and increasing cytosolic copper. This mutation triggers the expression of 13 secondary metabolite clusters, including cryptic pathways, during the whole developmental cycle, skipping the vegetative, non-productive stage. As a proof of concept, here, we tested whether the knockdown of the SCO2730/31 orthologue expression can enhance secondary metabolism in streptomycetes. We created a SCO2730/31 consensus antisense mRNA from the sequences of seven key streptomycetes, which helped to increase the cytosolic copper in S. coelicolor, albeit to a lower level than in the SCO2730::Tn5062 mutant. This antisense mRNA affected the production of at least six secondary metabolites (CDA, 2-methylisoborneol, undecylprodigiosin, tetrahydroxynaphtalene, α-actinorhodin, ε-actinorhodin) in the S. coelicolor, and five (phenanthroviridin, alkylresorcinol, chloramphenicol, pikromycin, jadomycin G) in the S. venezuelae; it also helped to alter the S. albus metabolome. The SCO2730/31 consensus antisense mRNA designed here constitutes a tool for the knockdown of SCO2730/31 expression and for the enhancement of Streptomyces’ secondary metabolism. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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23 pages, 2622 KiB

Open AccessArticle

Cross-Recognition of Promoters by the Nine SigB Homologues Present in Streptomyces coelicolor A3(2)

by Beatrica Sevcikova, Bronislava Rezuchova, Vladimira Mazurakova, Dagmar Homerova, Renata Novakova, Lubomira Feckova and Jan Kormanec

Int. J. Mol. Sci. 2021, 22(15), 7849; https://doi.org/10.3390/ijms22157849 - 22 Jul 2021

Cited by 4 | Viewed by 1788

Abstract

In contrast to Bacillus subtilis, Streptomyces coelicolor A3(2) contains nine homologues of stress response sigma factor SigB with a major role in differentiation and osmotic stress response. The aim of this study was to further characterize these SigB homologues. We previously established [...] Read more.

In contrast to Bacillus subtilis, Streptomyces coelicolor A3(2) contains nine homologues of stress response sigma factor SigB with a major role in differentiation and osmotic stress response. The aim of this study was to further characterize these SigB homologues. We previously established a two-plasmid system to identify promoters recognized by sigma factors and used it to identify promoters recognized by the three SigB homologues, SigF, SigG, and SigH from S. coelicolor A3(2). Here, we used this system to identify 14 promoters recognized by SigB. The promoters were verified in vivo in S. coelicolor A3(2) under osmotic stress conditions in sigB and sigH operon mutants, indicating some cross-recognition of these promoters by these two SigB homologues. This two-plasmid system was used to examine the recognition of all identified SigB-, SigF-, SigG-, and SigH-dependent promoters with all nine SigB homologues. The results confirmed this cross-recognition. Almost all 24 investigated promoters were recognized by two or more SigB homologues and data suggested some distinguishing groups of promoters recognized by these sigma factors. However, analysis of the promoters did not reveal any specific sequence characteristics for these recognition groups. All promoters showed high similarity in the -35 and -10 regions. Immunoblot analysis revealed the presence of SigB under osmotic stress conditions and SigH during morphological differentiation. Together with the phenotypic analysis of sigB and sigH operon mutants in S. coelicolor A3(2), the results suggest a dominant role for SigB in the osmotic stress response and a dual role for SigH in the osmotic stress response and morphological differentiation. These data suggest a complex regulation of the osmotic stress response in relation to morphological differentiation in S. coelicolor A3(2). Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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18 pages, 3902 KiB

Open AccessArticle

Definition of the Binding Architecture to a Target Promoter of HP1043, the Essential Master Regulator of Helicobacter pylori

by Annamaria Zannoni, Simone Pelliciari, Francesco Musiani, Federica Chiappori, Davide Roncarati and Vincenzo Scarlato

Int. J. Mol. Sci. 2021, 22(15), 7848; https://doi.org/10.3390/ijms22157848 - 22 Jul 2021

Cited by 8 | Viewed by 2283

Abstract

HP1043 is an essential orphan response regulator of Helicobacter pylori orchestrating multiple crucial cellular processes. Classified as a member of the OmpR/PhoB family of two-component systems, HP1043 exhibits a highly degenerate receiver domain and evolved to function independently of phosphorylation. Here, we investigated [...] Read more.

HP1043 is an essential orphan response regulator of Helicobacter pylori orchestrating multiple crucial cellular processes. Classified as a member of the OmpR/PhoB family of two-component systems, HP1043 exhibits a highly degenerate receiver domain and evolved to function independently of phosphorylation. Here, we investigated the HP1043 binding mode to a target sequence in the hp1227 promoter (P_hp1227). Scanning mutagenesis of HP1043 DNA-binding domain and consensus sequence led to the identification of residues relevant for the interaction of the protein with a target DNA. These determinants were used as restraints to guide a data-driven protein-DNA docking. Results suggested that, differently from most other response regulators of the same family, HP1043 binds in a head-to-head conformation to the P_hp1227 target promoter. HP1043 interacts with DNA largely through charged residues and contacts with both major and minor grooves of the DNA are required for a stable binding. Computational alanine scanning on molecular dynamics trajectory was performed to corroborate our findings. Additionally, in vitro transcription assays confirmed that HP1043 positively stimulates the activity of RNA polymerase. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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14 pages, 1601 KiB

Open AccessArticle

A Regulator Based “Semi-Targeted” Approach to Activate Silent Biosynthetic Gene Clusters

by Erik Mingyar, Lucas Mühling, Andreas Kulik, Anika Winkler, Daniel Wibberg, Jörn Kalinowski, Kai Blin, Tilmann Weber, Wolfgang Wohlleben and Evi Stegmann

Int. J. Mol. Sci. 2021, 22(14), 7567; https://doi.org/10.3390/ijms22147567 - 15 Jul 2021

Cited by 10 | Viewed by 3480

Abstract

By culturing microorganisms under standard laboratory conditions, most biosynthetic gene clusters (BGCs) are not expressed, and thus, the products are not produced. To explore this biosynthetic potential, we developed a novel “semi-targeted” approach focusing on activating “silent” BGCs by concurrently introducing a group [...] Read more.

By culturing microorganisms under standard laboratory conditions, most biosynthetic gene clusters (BGCs) are not expressed, and thus, the products are not produced. To explore this biosynthetic potential, we developed a novel “semi-targeted” approach focusing on activating “silent” BGCs by concurrently introducing a group of regulator genes into streptomycetes of the Tübingen strain collection. We constructed integrative plasmids containing two classes of regulatory genes under the control of the constitutive promoter ermE*p (cluster situated regulators (CSR) and Streptomyces antibiotic regulatory proteins (SARPs)). These plasmids were introduced into Streptomyces sp. TÜ17, Streptomyces sp. TÜ10 and Streptomyces sp. TÜ102. Introduction of the CSRs-plasmid into strain S. sp. TÜ17 activated the production of mayamycin A. By using the individual regulator genes, we proved that Aur1P, was responsible for the activation. In strain S. sp. TÜ102, the introduction of the SARP-plasmid triggered the production of a chartreusin-like compound. Insertion of the CSRs-plasmid into strain S. sp. TÜ10 resulted in activating the warkmycin-BGC. In both recombinants, activation of the BGCs was only possible through the simultaneous expression of aur1PR3 and griR in S. sp. TÜ102 and aur1P and pntR in of S. sp. TÜ10. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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15 pages, 1318 KiB

Open AccessArticle

The Low-Molecular Weight Protein Arginine Phosphatase PtpB Affects Nuclease Production, Cell Wall Integrity, and Uptake Rates of Staphylococcus aureus by Polymorphonuclear Leukocytes

by Mohamed Ibrahem Elhawy, Virginie Molle, Sören L. Becker and Markus Bischoff

Int. J. Mol. Sci. 2021, 22(10), 5342; https://doi.org/10.3390/ijms22105342 - 19 May 2021

Cited by 3 | Viewed by 2252

Abstract

The epidemiological success of Staphylococcus aureus as a versatile pathogen in mammals is largely attributed to its virulence factor repertoire and the sophisticated regulatory network controlling this virulon. Here we demonstrate that the low-molecular-weight protein arginine phosphatase PtpB contributes to this regulatory network [...] Read more.

The epidemiological success of Staphylococcus aureus as a versatile pathogen in mammals is largely attributed to its virulence factor repertoire and the sophisticated regulatory network controlling this virulon. Here we demonstrate that the low-molecular-weight protein arginine phosphatase PtpB contributes to this regulatory network by affecting the growth phase-dependent transcription of the virulence factor encoding genes/operons aur, nuc, and psmα, and that of the small regulatory RNA RNAIII. Inactivation of ptpB in S. aureus SA564 also significantly decreased the capacity of the mutant to degrade extracellular DNA, to hydrolyze proteins in the extracellular milieu, and to withstand Triton X-100 induced autolysis. SA564 ΔptpB mutant cells were additionally ingested faster by polymorphonuclear leukocytes in a whole blood phagocytosis assay, suggesting that PtpB contributes by several ways positively to the ability of S. aureus to evade host innate immunity. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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Review

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13 pages, 1018 KiB

Open AccessReview

Mechanisms of Action of Non-Canonical ECF Sigma Factors

by Francisco Javier Marcos-Torres, Aurelio Moraleda-Muñoz, Francisco Javier Contreras-Moreno, José Muñoz-Dorado and Juana Pérez

Int. J. Mol. Sci. 2022, 23(7), 3601; https://doi.org/10.3390/ijms23073601 - 25 Mar 2022

Cited by 7 | Viewed by 2000

Abstract

Extracytoplasmic function (ECF) sigma factors are subunits of the RNA polymerase specialized in activating the transcription of a subset of genes responding to a specific environmental condition. The signal-transduction pathways where they participate can be activated by diverse mechanisms. The most common mechanism [...] Read more.

Extracytoplasmic function (ECF) sigma factors are subunits of the RNA polymerase specialized in activating the transcription of a subset of genes responding to a specific environmental condition. The signal-transduction pathways where they participate can be activated by diverse mechanisms. The most common mechanism involves the action of a membrane-bound anti-sigma factor, which sequesters the ECF sigma factor, and releases it after the stimulus is sensed. However, despite most of these systems following this canonical regulation, there are many ECF sigma factors exhibiting a non-canonical regulatory mechanism. In this review, we aim to provide an updated and comprehensive view of the different activation mechanisms known for non-canonical ECF sigma factors, detailing their inclusion to the different phylogenetic groups and describing the mechanisms of regulation of some of their representative members such as EcfG from Rhodobacter sphaeroides, showing a partner-switch mechanism; EcfP from Vibrio parahaemolyticus, with a phosphorylation-dependent mechanism; or CorE from Myxococcus xanthus, regulated by a metal-sensing C-terminal extension. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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25 pages, 3215 KiB

Open AccessReview

Bacterial Transcriptional Regulators: A Road Map for Functional, Structural, and Biophysical Characterization

by Cristian M. Pis Diez, Maria Juliana Juncos, Matias Villarruel Dujovne and Daiana A. Capdevila

Int. J. Mol. Sci. 2022, 23(4), 2179; https://doi.org/10.3390/ijms23042179 - 16 Feb 2022

Cited by 8 | Viewed by 3282

Abstract

The different niches through which bacteria move during their life cycle require a fast response to the many environmental queues they encounter. The sensing of these stimuli and their correct response is driven primarily by transcriptional regulators. This kind of protein is involved [...] Read more.

The different niches through which bacteria move during their life cycle require a fast response to the many environmental queues they encounter. The sensing of these stimuli and their correct response is driven primarily by transcriptional regulators. This kind of protein is involved in sensing a wide array of chemical species, a process that ultimately leads to the regulation of gene transcription. The allosteric-coupling mechanism of sensing and regulation is a central aspect of biological systems and has become an important field of research during the last decades. In this review, we summarize the state-of-the-art techniques applied to unravel these complex mechanisms. We introduce a roadmap that may serve for experimental design, depending on the answers we seek and the initial information we have about the system of study. We also provide information on databases containing available structural information on each family of transcriptional regulators. Finally, we discuss the recent results of research about the allosteric mechanisms of sensing and regulation involving many transcriptional regulators of interest, highlighting multipronged strategies and novel experimental techniques. The aim of the experiments discussed here was to provide a better understanding at a molecular level of how bacteria adapt to the different environmental threats they face. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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16 pages, 1148 KiB

Open AccessReview

Affinity, Specificity, and Cooperativity of DNA Binding by Bacterial Gene Regulatory Proteins

by Jannette Carey

Int. J. Mol. Sci. 2022, 23(1), 562; https://doi.org/10.3390/ijms23010562 - 05 Jan 2022

Cited by 9 | Viewed by 2501

Abstract

Nearly all of biology depends on interactions between molecules: proteins with small molecules, proteins with other proteins, nucleic acids with small molecules, and nucleic acids with proteins that regulate gene expression, our concern in this Special Issue. All those kinds of interactions, and [...] Read more.

Nearly all of biology depends on interactions between molecules: proteins with small molecules, proteins with other proteins, nucleic acids with small molecules, and nucleic acids with proteins that regulate gene expression, our concern in this Special Issue. All those kinds of interactions, and others, constitute the vast majority of biology at the molecular level. An understanding of those interactions requires that we quantify them to learn how they interact: How strongly? With which partners? How—and how well—are different partners distinguished? This review addresses the evolution of our current understanding of the molecular origins of affinity and specificity in regulatory protein–DNA interactions, and suggests that both these properties can be modulated by cooperativity. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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15 pages, 1184 KiB

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The Regulatory Functions of σ⁵⁴ Factor in Phytopathogenic Bacteria

by Chao Yu, Fenghuan Yang, Dingrong Xue, Xiuna Wang and Huamin Chen

Int. J. Mol. Sci. 2021, 22(23), 12692; https://doi.org/10.3390/ijms222312692 - 24 Nov 2021

Cited by 9 | Viewed by 2229

Abstract

σ⁵⁴ factor (RpoN), a type of transcriptional regulatory factor, is widely found in pathogenic bacteria. It binds to core RNA polymerase (RNAP) and regulates the transcription of many functional genes in an enhancer-binding protein (EBP)-dependent manner. σ⁵⁴ has two conserved functional [...] Read more.

σ⁵⁴ factor (RpoN), a type of transcriptional regulatory factor, is widely found in pathogenic bacteria. It binds to core RNA polymerase (RNAP) and regulates the transcription of many functional genes in an enhancer-binding protein (EBP)-dependent manner. σ⁵⁴ has two conserved functional domains: the activator-interacting domain located at the N-terminal and the DNA-binding domain located at the C-terminal. RpoN directly binds to the highly conserved sequence, GGN₁₀GC, at the −24/−12 position relative to the transcription start site of target genes. In general, bacteria contain one or two RpoNs but multiple EBPs. A single RpoN can bind to different EBPs in order to regulate various biological functions. Thus, the overlapping and unique regulatory pathways of two RpoNs and multiple EBP-dependent regulatory pathways form a complex regulatory network in bacteria. However, the regulatory role of RpoN and EBPs is still poorly understood in phytopathogenic bacteria, which cause economically important crop diseases and pose a serious threat to world food security. In this review, we summarize the current knowledge on the regulatory function of RpoN, including swimming motility, flagella synthesis, bacterial growth, type IV pilus (T4Ps), twitching motility, type III secretion system (T3SS), and virulence-associated phenotypes in phytopathogenic bacteria. These findings and knowledge prove the key regulatory role of RpoN in bacterial growth and pathogenesis, as well as lay the groundwork for further elucidation of the complex regulatory network of RpoN in bacteria. Full article

(This article belongs to the Special Issue Bacterial Regulatory Proteins)

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