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At least 19 recordsLinked to original sources
PubMed1978

Delta factor can displace sigma factor from Bacillus subtilis RNA polymerase holoenzyme and regulate its initiation activity.

A protein with a molecular weight of 21,000 daltons is found associated with a fraction of Bacillus subtilis RNA polymerase core. This protein (delta) does not react with antibody made against sigma factor and has a peptide map which is significantly different from sigma factor. At ratios of 2:1 to 4:1 (delta:holoenzyme) the delta displaces sigma factor completely from the core and associates in a 1:1 ratio with core to form delta-core. Under the same incubation conditions sigma factor at a ratio of 10:1 (sigma factor:delta-core) does not displace delta from the delta-core. The delta-core has much less activity as compared to holoenzyme on various DNA templates. However, sigma factor does stimulate the activity of delta-core enzyme under conditions of RNA synthesis. These observations and the results of others suggest that delta-core enzyme binds initially to specific DNA sites followed by delta release from the core-DNA complex and that the sigma factor binds to the core-DNA complex to initiate RNA synthesis. Thus both delta and sigma factors are required in a sequential fashion for specific transcription to occur in B subtilis.

Bacillus subtilis↗
PubMed1979

Sigma factor is not released during transcription in Bacillus subtilis.

The relationship between sigma (sigma) and delta (delta) factors of Bacillus subtilis RNA polymerase has been analyzed during initiation of RNA synthesis. When core enzyme (E) containing delta factor (E delta) binds to DNA, the delta factor is released with the formation of an E-DNA complex. The addition of sigma to the E-DNA complex results in the formation of a stable E sigma-DNA complex which can synthesize RNA upon addition of nucleoside triphosphates. Sigma factor, significantly, is not released from the core during RNA synthesis. These results suggest that delta and sigma factors can act sequentially during initiation of RNA synthesis with delta acting as a DNA recognition factor and sigma acting as an initiation factor. The results do not preclude the possibility that E sigma can initiate RNA synthesis correctly since E sigma alone can bind to DNA and initiate RNA synthesis.

Bacillus subtilis↗
PubMed2025

WhiB6 Transduces Contact-Dependent Signaling in Mycobacterium smegmatis and Coordinately Induces Both ESX-1 and ESX-4.

Bacteria have evolved complex conditional pathways that respond to environmental stresses and signals. We use conjugation in Mycobacterium smegmatis to identify contact-recognition and response pathways that mediate interactions between donor and recipient cells. Contact with a compatible donor cell initiates a response in the recipient that requires the ESX-1 secretion system and subsequently activates the dormant ESX-4 secretion system. The links of this signal transduction pathway, the mechanism of coordination and dependency between ESX-1 and ESX-4 secretion systems, are unknown. Previous studies identified SigM as a cell-contact responsive sigma factor dedicated to activating ESX-4. WhiB proteins are iron-sulfur-binding stress-response transcription factors exclusively found in Actinobacteria. WhiB6 has been shown to regulate ESX-1 associated gene expression in other mycobacteria. Here, we show that WhiB6 is required both for conjugation and for transducing cell-contact dependent signaling in the recipient cell. Our RNA-seq, ChIP-seq, and proteomic profiling data define a WhiB6 regulon that supports conjugative cell-cell interaction. The WhiB6 regulon includes genes encoding ESX-1, ESX-4, SigM, as well as dispersed operons that likely support ESX secretion. Our data demonstrate that WhiB6 is epistatic to SigM and ESX-4 in this signal transduction pathway. This work shows that WhiB6 functions as a signal transduction node in recipient cells: it coordinates the expression of two ESX systems and it also induces uncharacterized proteins that collectively constitute a complete secretion response to recipient contact with a donor cell.

Mycobacterium smegmatis↗
PubMed2026

A conserved partner-switching system controls terminal differentiation in multicellular cyanobacteria.

UNLABELLED: Canonical partner-switching systems (PSSs) regulate sigma factor activity through reversible phosphorylation, but their established roles have been largely limited to stress responses and sporulation in Firmicutes. Whether this regulatory mechanism also controls developmental cell fate decisions in other bacterial phyla has remained unknown. Here, we identify a canonical PSS that governs heterocyst differentiation in the multicellular cyanobacterium Anabaena sp. PCC 7120. This system comprises the anti-sigma factor All2284 (NfsS) and the anti-anti-sigma factor All2283 (NfsR). Structural predictions and biochemical assays showed that NfsS phosphorylates NfsR on a conserved serine residue, whereas bacterial two-hybrid and co-purification assays demonstrated that NfsS binds the developmental sigma factors SigC and SigE. Deletion of nfsR abolished heterocyst formation and diazotrophic growth, and transcriptomic analysis revealed broad failure to induce late heterocyst genes, including nitrogen fixation functions such as nifHDK and fdxH. Phylum-wide comparative genomics further showed that PSS genes and putative functional clusters are strongly enriched in filamentous and heterocyst-forming taxa, indicating an association between the expansion of these signaling modules and the emergence of multicellularity and developmental specialization. Together, these findings establish a PSS as a direct regulator of terminal cell differentiation in a gram-negative bacterium and reveal partner switching as a conserved regulatory principle linking environmental signaling to developmental fate in a major bacterial phylum. IMPORTANCE: While partner-switching systems are classically associated with stress responses and sporulation control in Firmicutes, whether this regulatory logic governs developmental decisions in other bacterial phyla has remained unknown. Here, we establish that a related partner-switching mechanism operates in a distinct bacterial lineage, the cyanobacteria, where it controls a major developmental transition involving terminal cell differentiation. Specifically, we show that a phosphorylation-dependent checkpoint involving the anti-sigma factor NfsS and the anti-anti-sigma factor NfsR directly regulates heterocyst formation. Disruption of this switch abolishes cell differentiation and diazotrophic growth, revealing that this system is an obligate gatekeeper for terminal differentiation. Conceptually, these findings substantially extend the known functional repertoire of partner-switching circuits: rather than controlling stress adaptation or spore dormancy, this module has been co-opted to govern a complex, multicellular developmental program in an organism that underpins global carbon and nitrogen cycles. This work, therefore, establishes a new paradigm for phosphorylation-based control of developmental sigma factors and provides a tractable model for dissecting how conserved signaling modules are rewired to drive lineage-specific innovations across the bacterial domain.

cell differentiation↗
PubMed2026

Paradigm shift for cry gene expression in Bacillus thuringiensis.

In most Bacillus thuringiensis strains, the cry genes are transcribed by RNA polymerases containing sporulation-sigma factors E or K, leading to the formation of an insecticidal crystal within the mother cell along spore development. The kurstaki HD1 strain, a parent of commercial strains, also releases the insecticidal proteins Cry1I and Vip3A in the extracellular medium. vip3A expression is activated by the transcriptional regulator VipR at the onset of the stationary phase. Here, we expanded the VipR regulon in strain HD1 by identifying the VipR-binding box upstream from the cry2Aa, cry2Ab, and cry1Ia genes, and conducting transcription assays. Unexpectedly, a VipR box was located in the promoter of a putative N-acetylmuramoyl-l-alanine amidase (ami) gene upstream from cry1Ac in strain kurstaki HD73, closely related to the HD1 but devoid of vipR. Introduction of vipR in this strain led to the expression of the ami-cry1Ac operon, resulting in an early and increased production of Cry1Ac. We demonstrated that Cry1Ac was also produced in a VipR-dependent manner in an HD73 ∆spo0A mutant. Similarly, an HD1 ∆spo0A strain produces all the insecticidal proteins encoded in its genome, including cry2Ab, previously considered unexpressed. A genomic analysis also revealed the presence of putative VipR-binding sequences in lepidopteran-active strains, upstream from cry genes such as cry1E, cry1F, cry9D, and cry9E. Overall, our results break the dogma on the regulation of cry1A and cry2A genes and provide evidence of sporulation-independent Cry toxin production in biopesticidal Bt strains.IMPORTANCEBacillus thuringiensis is a remarkably efficient entomopathogen due to its ability to produce various insecticidal proteins, such as Cry or Vip. This property has made it a highly effective biopesticide used worldwide. Our work modifies the paradigm of cry1 and cry2 genes being regulated solely by sporulation-specific sigma factors and thus exclusively expressed during this process. Indeed, we demonstrated that the VipR regulator controls the transcription of vip3Aa, cry2Aa, cry2Ab, cry1Ia, and the ami-cry1A operons encoded by a strain closely related to that of commercial biopesticides and specifically turns on their expression from the onset of the stationary phase, leading to the production of insecticidal crystals independently of sporulation. By providing new knowledge on the regulation of insecticidal protein genes, these findings bring new insight for the genetic improvement of Bt strains used as commercial biopesticides.

Bacillus thuringiensis↗
PubMed2026

A single DNA methylation site regulates cell fate during Clostridioides difficile sporulation.

DNA methylation is a widespread phenomenon in bacteria that can regulate gene expression, although the mechanisms underlying this epigenetic regulation are often poorly understood. In Clostridioides difficile, the orphan DNA methyltransferase CamA promotes sporulation, a process critical for the persistence and transmission of this nosocomial pathogen. However, the specific CamA target genes that drive this increased sporulation phenotype were unknown. Here, we show that methylation of a single CamA motif in the promoter region of spoIIE, which encodes a factor critical for activating the early-acting sporulation sigma factor, σF, is sufficient to promote spoIIE transcription, σF activation, and spore formation. Surprisingly, the CamA-dependent increase in spoIIE expression also increases the frequency with which cells prematurely activate σF prior to asymmetric division, resulting in miscompartmentalized σF activity. While this premature activation event triggers cell lysis in the well-studied spore-former Bacillus subtilis, we show that C. difficile cells retain developmental plasticity: predivisional cells that have prematurely activated σF can abort sporulation and resume vegetative growth, whereas cells that activate σF in the forespore after asymmetric division remain committed to sporulation. Thus, DNA methylation controls a critical cell fate decision in C. difficile without compromising its capacity to adapt to fluctuating environmental conditions. Finally, we show that CamA confers a significant fitness advantage during murine infection through mechanisms largely independent of its ability to promote sporulation. Since CamA is specific to C. difficile and epigenetically regulates multiple pathways critical for pathogen persistence, these analyses imply that CamA could be a promising antimicrobial target.

DNA Methylation↗
PubMed2017

The Influence of the Toxin/Antitoxin mazEF on Growth and Survival of Listeria monocytogenes under Stress.

A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σB). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σB operon in L. monocytogenes is the TA system mazEF, which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added. Growth of a ΔmazEF mutant was enhanced relative to the wildtype in the presence of sub-inhibitory norfloxacin and at 42 °C, but was decreased when challenged with ampicillin and gentamicin. In contrast to studies in Staphylococcus aureus, we found that the mazEF locus did not affect transcription of genes within the σB operon, but MazEF effected the expression of the σB-dependent genes opuCA and lmo0880, with a 0.22 and 0.05 fold change, respectively, compared to the wildtype under sub-inhibitory norfloxacin conditions. How exactly this system operates remains an open question, however, our data indicates it is not analogous to the system of S. aureus, suggesting a novel mode of action for MazEF in L. monocytogenes.

Anti-Bacterial Agents↗
PubMed2025

The SinR·SlrR Heteromer Attenuates Transcription of a Long Operon of Flagellar Genes in Bacillus subtilis.

During growth, Bacillus subtilis differentiates into subpopulations of motile individuals and non-motile chains, associated with dispersal and biofilm formation, respectively. The two cell types are dictated by the activity of the alternative sigma factor SigD encoded as the penultimate gene of the 27-kb long fla/che flagellar operon. The frequency of SigD-ON motile cells is increased by the heteromeric transcription factor SwrA·DegU that activates the fla/che promoter. Conversely, the frequency of motile cells is decreased by the heteromeric transcription factor SinR·SlrR, but the mechanism and location of inhibition is poorly understood. Here, using ChIP-Seq analysis, we determine the binding sites of the SinR·SlrR heteromer on the genome. We identified two sites within the fla/che operon that were necessary and sufficient to attenuate transcript abundance by causing premature termination upstream of the gene that encodes SigD. Thus, cell motility and the transition to biofilm formation depend on the expression of a long operon governed by two opposing heteromeric transcription factors that operate at two different stages of the transcription cycle. More broadly, our study serves as a model for transcription factors that control transcriptional elongation and the regulation of long operons in bacteria.

Bacillus subtilis↗
PubMed1979

Distinctive nucleotide sequences of promoters recognized by RNA polymerase containing a phage-coded "sigma-like" protein.

We report the nucleotide sequences of two promoters for bacteriophage SP01 "middle" genes. These promoters are recognized by a modified form of Bacillus subtilis RNA polymerase that contains a phage-coded "sigma-like" regulatory protein (gp28) in place of the bacterial sigma factor. Both promoters shared the identical hexanucleotide 5'A-G-G-A-G-A at about 35 base pairs preceding the start point of transcription and the identical heptanucleotide 5'-T-T-T-A-T-T-T (T is the thymine analog 5-hydroxymethyluracil in SP01 DNA) located about 10 base pairs preceding the transcriptional start point. The significance of these sequences in comparison with nucleotide sequences of promoters recognized by sigma-containing RNA polymerases is discussed.

Bacillus subtilis↗
PubMed2025

Variability in intrinsic promoter strength underlies the temporal hierarchy of the Caulobacter SOS response induction.

Bacteria encode for gene regulatory networks crucial for sensing and repairing DNA damage. Upon exposure to genotoxic stress, these transcriptional networks are induced in a temporally structured manner. A case in point is of the highly conserved SOS response that is regulated by the LexA repressor. Studies have proposed that affinity of LexA towards promoters of SOS response genes is the primary determinant of its expression dynamics. Here, we describe an additional level of regulation beyond LexA box properties that modulates the SOS response gene expression pattern. Using transcriptomic analyses, we reveal a distinct temporal hierarchy in the induction of SOS-regulated genes in Caulobacter crescentus. We observe that LexA box properties are insufficient in predicting the temporal hierarchy of these genes. Instead, we find that intrinsic promoter strength underlies the order of gene activation, with differential sigma factor association as one of the factors modulating gene expression timing. Our findings highlight a novel regulatory layer in SOS dynamics and underscore the importance of promoter properties in shaping bacterial stress responses.

Promoter Regions, Genetic↗
PubMed2026

Comparative Characterization of σ32-Dependent Promoters for the Heat-Inducible Expression of FAST-PETase in Escherichia coli.

Efficient regulation of recombinant enzyme expression is an important consideration for the development of microbial biocatalysts. Heat-inducible promoters regulated by the alternative sigma factor σ32 provide an inducer-free strategy for controlling gene expression in Escherichia coli. In this study, four σ32-dependent promoters (PdnaK, PgrpE, PibpA, and PclpB) were comparatively characterized using the PET-degrading enzyme FAST-PETase fused to superfolder green fluorescent protein as a model recombinant protein. Promoter performance was evaluated based on basal leakage, induction kinetics, and expression strength following heat induction. Among the promoters examined, PdnaK exhibited the strongest heat-inducible expression and was dissected to examine the autonomous and combinatorial behavior of its promoter-derived elements. Molecular docking analysis further supported the experimental observations by showing qualitative agreement between predicted σ32-DNA interactions and promoter performance. Together, these findings provide a comparative characterization of σ32-dependent promoters and identify promoter architectures that may facilitate the development of heat-inducible recombinant enzyme expression systems in E. coli.

Escherichia coli↗
PubMed2025

Symbionts with eroded genomes adjust gene expression according to host life-stage and environment.

Symbiotic bacteria in long-term host associations frequently undergo extreme genome reduction. While they retain genes beneficial to the host, their repertoire of transcription factors is severely reduced. Here, we assessed whether genome-eroded symbionts can still regulate gene expression by characterizing the transcriptional responses of obligate symbionts in reed beetles to different temperatures and host life stages. These symbionts feature a small genome (~0.5 Mb), encoding for 9-10 essential amino acid biosynthesis pathways, 0-2 pectinases, and 4-5 transcription factors. We found that the symbionts respond to winter conditions by upregulating a heat-shock sigma factor and downregulating translation machinery. Across life stages, symbionts adjusted gene expression to meet the hosts' nutritional demands, upregulating amino acid biosynthesis in larvae, while expression and activity of host and symbiont enzymes involved in plant cell wall breakdown increased in the folivorous adults. In addition, the regulation of symbiont cell morphology genes corresponded to cell shape differences across life stages. Thus, reed beetle symbionts may use their few transcription factors to respond to the host's environment, highlighting the regulatory potential of long-term coevolved symbionts despite severely reduced genomes.

Symbiosis↗
PubMed2026

Azotobacter vinelandii AmrZ is a global regulator linking alginate production and c-di-GMP homeostasis.

Azotobacter vinelandii, a member of the Pseudomonadaceae, produces the exopolysaccharide alginate during vegetative growth; however, the circuitry linking alginate biosynthesis to lifestyle transitions remains poorly defined. Here, we show that the Ribbon-Helix-Helix transcription factor AmrZ coordinates alginate production, intracellular c-di-GMP levels and motility. Deletion of amrZ abolished alginate synthesis, whereas chromosomal complementation restored it. A PalgD-gusA fusion and RT-qPCR demonstrated that algD, the first gene in the alginate biosynthetic cluster, depends on AmrZ for expression. Motif analysis identified multiple AmrZ sites upstream of algD, and electrophoretic mobility-shift assays (EMSAs) confirmed specific binding to these regions. AmrZ also positively autoregulates: PamrZ-gusA activity decreased in ΔamrZ, and purified AmrZ bound the amrZ promoter in EMSA. Moreover, PamrZ activity required the sigma factor AlgU, consistent with the presence of an AlgU promoter; this positive, AlgU-dependent feedback may stabilize AmrZ under alginate-inducing conditions. To probe AmrZ control of c-di-GMP, we implemented a riboswitch-based biosensor in A. vinelandii. The ΔamrZ strain showed a markedly reduced signal, similar to a diguanylate cyclase (DGC) mutant, whereas a phosphodiesterase mutant displayed elevated output, validating the assay. RNA-seq and RT-qPCR identified two DGC genes, AVAEIV_RS11610 and AVAEIV_RS18795, as AmrZ-activated targets; EMSA verified direct binding at the RS11610 regulatory region. By contrast, transcription of the principal vegetative DGC AvGReg was not AmrZ-regulated. Lower c-di-GMP in ΔamrZ correlated with larger swimming halos. Collectively, these genetic, biochemical and transcriptomic data support a model in which AmrZ directly activates algD and elevates c-di-GMP via selected DGCs, thereby promoting alginate synthesis while reducing motility. RNA-seq data also indicate that AmrZ influences broader cellular programmes, including metabolism and iron homeostasis, positioning AmrZ as a central regulator that links c-di-GMP homeostasis to coordinated exopolysaccharide production in A. vinelandii. This work contributes to our understanding of the regulatory networks controlled by AmrZ outside the Pseudomonas genus and reveals important differences in its targets and regulatory mechanisms.

Azotobacter vinelandii↗
PubMed2025

Autoregulation of the Master Regulator Spo0A Controls Cell-Fate Decisions in Bacillus subtilis.

Spo0A in Bacillus subtilis is activated by phosphorylation (Spo0A~P) upon starvation and differentially controls a set of genes involved in biofilm formation and sporulation. The spo0A gene is transcribed by two distinct promoters, a σA-recognized upstream promoter Pv during growth, and a σH-recognized downstream promoter Ps during starvation, and appears to be autoregulated by four Spo0A~P binding sites (0A1-4 boxes) localized between two promoters. However, the autoregulatory mechanisms and their impact on differentiation remain elusive. Here, we determined the relative affinity of Spo0A~P for each 0A box and dissected each promoter in combination with the systematic 0A box mutations. The data revealed that (1) the Pv and Ps promoters are on and off, respectively, under nutrient-rich conditions without Spo0A~P, (2) the Ps promoter is activated by first 0A3 and then 0A1 during early starvation with low Spo0A~P, (3) during later starvation with high Spo0A~P, the Pv promoter is repressed by first 0A1 and then 0A2 and 0A4, and (4) during prolonged starvation, both promoters are silenced by all 0A boxes with very high Spo0A~P. Our results indicate that the autoregulation of spo0A is one of the key determinants to achieve a developmental increase in Spo0A~P, leading to a temporal window for entry into biofilm formation or sporulation.

Bacillus subtilis↗
PubMed2026

Rop-Mediated Suppression of RpoS Production Increases Resistance to Nitric Oxide.

We identified the RNA-binding protein Rop, encoded on the pOSAK1 plasmid of enterohaemorrhagic Escherichia coli (EHEC), as a novel factor that enhances nitric oxide (NO) resistance, although it has previously been reported to regulate plasmid copy number. The Rop-induced increase in NO resistance was significantly reduced in several small noncoding RNA (sRNA) gene-deficient EHEC mutants. Among these sRNAs, DsrA, ArcZ, and RprA were directly involved in the translational regulation of rpoS expression, suggesting that Rop modulates rpoS expression through sRNAs. To examine this mechanism, we generated sRNA gene-deficient mutants with an additional deletion of the 5' untranslated region (5' UTR) of rpoS, which is required for translational regulation. The increase in NO resistance by Rop was restored in the double mutant, suggesting that this phenotype is mediated by Rop-dependent interactions between sRNAs and the 5' UTR of rpoS mRNA. Furthermore, Rop promoted rpoS mRNA degradation, an effect that likely suppresses RpoS production and may thereby enhance NO resistance. Finally, an hfq-deficient EHEC mutant exhibited no increase in NO resistance in the presence of Rop, indicating that Hfq is essential for Rop-mediated NO resistance.

Nitric Oxide↗
PubMed2025

Rapid screening and identification of genes involved in bacterial extracellular membrane vesicle production using a curvature-sensing peptide.

Bacteria secrete extracellular membrane vesicles (EMVs). Physiological functions and biotechnological applications of these lipid nanoparticles have been attracting significant attention. However, the details of the molecular basis of EMV biogenesis have not yet been fully elucidated. In our previous work, an N-terminus-substituted FAAV peptide labeled with nitrobenzoxadiazole (NBD; nFAAV5-NBD) was developed. This peptide can sense the curvature of a lipid bilayer and selectively bind to EMVs even in the presence of cells. Here, we applied nFAAV5-NBD to a genome-wide screening of hyper- and hypo-vesiculation transposon mutants of a Gram-negative bacterium, Shewanella vesiculosa HM13, to identify the genes involved in EMV production. We analyzed the transposon insertion sites in hyper- and hypo-vesiculation mutants and identified 16 and six genes, respectively, with a transposon inserted within or near them. Targeted gene-disrupted mutants of the identified genes showed that the lack of putative dipeptidyl carboxypeptidase, glutamate synthase β-subunit, LapG protease, metallohydrolase, RNA polymerase sigma-54 factor, inactive transglutaminase, PepSY domain-containing protein, and Rhs-family protein caused EMV overproduction. On the other hand, disruption of the genes encoding putative phosphoenolpyruvate synthase, d-hexose-6-phosphate epimerase, NAD-specific glutamate dehydrogenase, and sensory box histidine kinase/response regulator decreased EMV production. This study demonstrates the utility of a novel screening method using a curvature-sensing peptide for mutants with altered EMV productivity and provides information on the genes related to EMV production.IMPORTANCEConventional methods for isolation and quantification of extracellular membrane vesicles (EMVs) are generally time-consuming. nFAAV5-NBD can detect EMVs in the culture without separating EMVs from cells. In situ detection of EMVs using this peptide facilitated screening of the genes related to EMV production. We succeeded in identifying various genes associated with EMV production of Shewanella vesiculosa HM13, which would contribute to the elucidation of bacterial EMV formation mechanisms. Additionally, the hyper-vesiculating mutants obtained in this study would be valuable for EMV applications, such as secreting useful substances as EMV cargoes and producing artificially functionalized EMVs.

Shewanella↗