RESUMO
Parkinson's disease is characterized by the deposition of α-synuclein, which leads to synaptic dysfunction, the loss of neuronal connections and ultimately progressive neurodegeneration. Despite extensive research into Parkinson's disease pathogenesis, the mechanisms underlying α-synuclein-mediated synaptopathy have remained elusive. Several lines of evidence suggest that altered nicotinamide adenine dinucleotide (NAD+) metabolism might be causally related to synucleinopathies, including Parkinson's disease. NAD+ metabolism is central to the maintenance of synaptic structure and function. Its synthesis is mediated by nicotinamide mononucleotide adenylyltransferases (NMNATs), but their role in Parkinson's disease is not known. Here we report significantly decreased levels of NMNAT3 protein in the caudate nucleus of patients who have died with Parkinson's disease, which inversely correlated with the amount of monomeric α-synuclein. The detected alterations were specific and significant as the expression levels of NMNAT1, NMNAT2 and sterile alpha and TIR motif containing 1 (SARM1) were not significantly different in Parkinson's disease patients compared to controls. To test the functional significance of these findings, we ectopically expressed wild-type α-synuclein in retinoic acid-differentiated dopaminergic SH-SY5Y cells that resulted in decreased levels of NMNAT3 protein plus a neurite pathology, which could be rescued by FK866, an inhibitor of nicotinamide phosphoribosyltransferase that acts as a key enzyme in the regulation of NAD+ synthesis. Our results establish, for the first time, NMNAT3 alterations in Parkinson's disease and demonstrate in human cells that this phenotype together with neurite pathology is causally related to α-synucleinopathy. These findings identify alterations in the NAD+ biosynthetic pathway as a pathogenic mechanism underlying α-synuclein-mediated synaptopathy.
Assuntos
Neuroblastoma , Nicotinamida-Nucleotídeo Adenililtransferase , Doença de Parkinson , Sinucleinopatias , Neurônios Dopaminérgicos/metabolismo , Humanos , NAD/metabolismo , Neuritos/metabolismo , Neuroblastoma/metabolismo , Nicotinamida-Nucleotídeo Adenililtransferase/genética , Nicotinamida-Nucleotídeo Adenililtransferase/metabolismo , Doença de Parkinson/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
RNA interference (RNAi) methods for insects are often limited by problems with double-stranded (ds) RNA delivery, which restricts reverse genetics studies and the development of RNAi-based biocides. We therefore delegated to insect symbiotic bacteria the task of: (i) constitutive dsRNA synthesis and (ii) trauma-free delivery. RNaseIII-deficient, dsRNA-expressing bacterial strains were created from the symbionts of two very diverse pest species: a long-lived blood-sucking bug, Rhodnius prolixus, and a short-lived globally invasive polyphagous agricultural pest, western flower thrips (Frankliniella occidentalis). When ingested, the manipulated bacteria colonized the insects, successfully competed with the wild-type microflora, and sustainably mediated systemic knockdown phenotypes that were horizontally transmissible. This represents a significant advance in the ability to deliver RNAi, potentially to a large range of non-model insects.
Assuntos
Marcação de Genes/métodos , Interferência de RNA , RNA de Cadeia Dupla/genética , Rhodnius/genética , Rhodococcus/genética , Tisanópteros/genética , Animais , Rhodnius/microbiologia , Análise de Sequência de DNA , Simbiose , Tisanópteros/microbiologiaRESUMO
Dps proteins are members of an extensive family of proteins that oxidise and deposit iron in the form of ferric oxide, and are also able to bind DNA. Ferroxidation centres are formed at the interface of anti-parallel dimers, which further assemble into dodecameric nanocages with a hollow core where ferric oxide is deposited. Streptomyces coelicolor encodes three Dps-like proteins (DpsA, B and C). Despite sharing the conserved four-helix bundle organisation observed in members of the Dps family, they display significant differences in the length of terminal extensions, or tails. DpsA possess both N- and C-terminal tails of different lengths, and their removal affects quaternary structure assembly to varying degrees. DpsC quaternary structure, on the other hand, is heavily dependent on its N-terminal tail as its removal abolishes correct protein folding. Analysis of the crystal structure of dodecamers from both proteins revealed remarkable differences in the position of tails and interface surface area; and provides insight to explain the differences in biochemical behaviour observed while comparing DpsA and DpsC.
Assuntos
Proteínas de Bactérias/química , Proteínas de Ligação a DNA/química , Proteínas Recombinantes/química , Streptomyces coelicolor/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cristalização , Cristalografia por Raios X , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Eletroforese em Gel de Poliacrilamida , Escherichia coli/genética , Ferro/química , Ferro/metabolismo , Modelos Moleculares , Mutação , Ligação Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Multimerização Proteica , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Streptomyces coelicolor/genéticaRESUMO
Antibiotic-producing Streptomyces are complex bacteria that remodel global transcription patterns and their nucleoids during development. Here, we describe a novel developmentally regulated nucleoid-associated protein, DdbA, of the genus that consists of an N-terminal DNA-binding histone H1-like domain and a C-terminal DksA-like domain that can potentially modulate RNA polymerase activity in conjunction with ppGpp. Owing to its N-terminal domain, the protein can efficiently bind and condense DNA in vitro. Loss of function of this DNA-binding protein results in changes in both DNA condensation during development and the ability to adjust DNA supercoiling in response to osmotic stress. Initial analysis of the DksA-like activity of DdbA indicates that overexpression of the protein suppresses a conditional deficiency in antibiotic production of relA mutants that are unable to synthesise ppGpp, just as DksA overexpression in Escherichia coli can suppress ppGpp(0) phenotypes. The null mutant is also sensitive to oxidative stress owing to impaired upregulation of transcription of sigR, encoding an alternative sigma factor. Consequently, we propose this bifunctional histone-like protein as a candidate that could structurally couple changes in DNA conformation and transcription during the streptomycete life-cycle and in response to stress.
Assuntos
DNA Fúngico/química , Proteínas Fúngicas/metabolismo , Histonas/metabolismo , Streptomyces coelicolor/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Fúngicas/química , Guanosina Tetrafosfato/biossíntese , Histonas/química , Ligases/genética , Conformação de Ácido Nucleico , Pressão Osmótica , Estrutura Terciária de Proteína , Esporos Fúngicos/fisiologia , Streptomyces coelicolor/crescimento & desenvolvimento , Streptomyces coelicolor/fisiologia , Estresse Fisiológico/genética , Transcrição GênicaRESUMO
Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically.
Assuntos
Metabolismo Energético/genética , Neoplasias/genética , Nicotinamida N-Metiltransferase/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Desintoxicação Metabólica Fase II/genética , NAD/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Processamento de Proteína Pós-Traducional/genéticaRESUMO
The anti-inflammatory and cholesterol lowering capabilities of probiotic bacteria highlight them as potential prophylactics against chronic inflammatory diseases, particularly cardiovascular disease. Previous studies in silico, in vitro, and in vivo suggest that the Lab4 probiotic consortium may harbour such capabilities and in the current study, we assessed plasma levels of cytokines/chemokines, short chain fatty acids and lipids and faecal levels of bile acids in a subpopulation of healthy Wistar rats included in 90-day repeat dose oral toxicity study. In the rats receiving Lab4, circulating levels of pro-inflammatory interleukin-6, tumour necrosis factor-α and keratinocyte chemoattractant/growth regulated oncogene were significantly lower compared to the control group demonstrating a systemic anti-inflammatory effect. These changes occurred alongside significant reductions in plasma low density lipoprotein cholesterol and increases in faecal bile acid excretion implying the ability to lower circulating cholesterol via the deconjugation of intestinal bile acids. Correlative analysis identified significant associations between plasma tumour necrosis factor-α and the plasma total cholesterol:high density lipoprotein cholesterol ratio and faecal levels of bifidobacteria in the Lab4 rats. Together, these data highlight Lab4 supplementation as a holistic approach to CVD prevention and encourages further studies in humans.
RESUMO
An esx locus, related to the multiple esx loci of Mycobacterium tuberculosis, is conserved in all sequenced Streptomyces genomes, where it is associated with the developmental regulatory gene bldB. Here we demonstrate that the esxBA operon, comprising part of the locus, has a novel morphogenetic function in the model species Streptomyces coelicolor. This operon encodes two proteins belonging to the WXG-100 superfamily that can form a heterodimer and are secreted in the absence of signal sequences. A mutation in esxBA results in a delay in sporulation, with eventual development of aerial hyphae with chains of abnormally sized spore compartments possessing irregular DNA contents. During early sporulation, expression of the operon is elevated in a bldB mutant. Other genes in the locus, notably SCO5734 and SCO5721, encode components of a type VII secretion system. Disruption of either of these genes prevents secretion of EsxAB but has no effect on sporulation. To explain the morphogenetic function of EsxAB, we propose that the heterodimer sequesters a regulator of expression of genes involved in nucleoid organization during sporulation.
Assuntos
Proteínas de Bactérias/metabolismo , Streptomyces coelicolor/metabolismo , Sequência de Bases , Dimerização , Mutação , Óperon , Streptomyces coelicolor/genética , Streptomyces coelicolor/crescimento & desenvolvimentoRESUMO
In an effort to stem the rising tide of multi-resistant bacteria, researchers have turned to niche environments in the hope of discovering new varieties of antibiotics. We investigated an ethnopharmacological (cure) from an alkaline/radon soil in the area of Boho, in the Fermanagh Scarplands (N. Ireland) for the presence of Streptomyces, a well-known producer of antibiotics. From this soil we isolated a novel (closest relative 57% of genome relatedness) Streptomyces sp. capable of growth at high alkaline pH (10.5) and tolerant of gamma radiation to 4 kGy. Genomic sequencing identified many alkaline tolerance (antiporter/multi-resistance) genes compared to S. coelicolor M145 (at 3:1), hence we designated the strain Streptomyces sp. myrophorea, isolate McG1, from the Greek, myro (fragrance) and phorea (porter/carrier). In vitro tests demonstrated the ability of the Streptomyces sp. myrophorea, isolate McG1 to inhibit the growth of many strains of ESKAPE pathogens; most notably carbapenem-resistant Acinetobacter baumannii (a critical pathogen on the WHO priority list of antibiotic-resistant bacteria), vancomycin-resistant Enterococcus faecium, and methicillin-resistant Staphylococcus aureus (both listed as high priority pathogens). Further in silico prediction of antimicrobial potential of Streptomyces sp. myrophorea, isolate McG1 by anti-SMASH and RAST software identified many secondary metabolite and toxicity resistance gene clusters (45 and 27, respectively) as well as many antibiotic resistance genes potentially related to antibiotic production. Follow-up in vitro tests show that the Streptomyces sp. myrophorea, isolate McG1 was resistant to 28 out of 36 clinical antibiotics. Although not a comprehensive analysis, we think that some of the Boho soils' reputed curative properties may be linked to the ability of Streptomyces sp. myrophorea, isolate McG1 to inhibit ESKAPE pathogens. More importantly, further analysis may elucidate other key components that could alleviate the tide of multi-resistant nosocomial infections.
RESUMO
A novel actinobacterial strain, designated S10T, was isolated from a sand sample collected from the Qaidam Basin in Qinghai province, China. The strain S10T exhibited antibacterial activity against MRSA. The taxonomic position of the strain S10T was determined by a polyphasic approach. There were six copies of 16S rDNA in S10T which were not same exactly (MH257693-MH257698). Phylogenetic analysis of 16S rRNA gene sequences indicated the strain belonging to the genus Streptomyces and it showed high sequence similarities with Streptomyces chartreusis NBRC 12753T (99.31%), Streptomyces phaeoluteigriseus DSM 41896T (99.24%), Streptomyces variegatus NRRL B-16380T (99.17%) and Streptomyces flavovariabilis NRRL B-16367T (99.17%) comparing with MH257693, MH257695, MH257696, MH257697, and MH257698. Similarities with Streptomyces kunmingensis NBRC14463T (98.82%), Streptomyces bungoensis DSM 41781T(98.76%), S. chartreusis NBRC 12753T (98.69%) and S. phaeoluteigriseus DSM 41896T (98.62%) with MH257694. Whole-genome average nucleotide identity (ANI) values between strain S10T and S. chartreusis NBRC 12753T, S. phaeoluteigriseus DSM 41896T, S. variegatus NRRL B-16380T, S. flavovariabilis NRRL B-16367T, S. kunmingensis NBRC 14463T, S. bungoensis DSM 41781T were 83.63%, 82.89%, 92.55%, 92.51%, 79.29, and 82.87%, respectively, suggesting that the strain S10T represented a new species. A phylogenetic analysis comparing the S10T genome with those of 336 other sequenced Streptomyces genomes confirmed its relatedness with Streptomyces variegatus NRRL B-16380T and Streptomyces flavovariabilis NRRL B-16367T. Strain S10T contained LL-diaminopimelic acid in the cell wall. The predominant menaquinones were MK-9(H6) and MK-9(H8) and the major fatty acids were iso-C15:0, anteiso-C15:0, iso-C16:0, and anteiso-C17:0. Phospholipids detected were diphosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl choline, three unknown phospholipids, an unknown aminophospholipid and an unknown phosphatidyl glycolipid. On the basis of these genotypic and phenotypic data, it is proposed that isolate S10T (=JCM 31184T =CGMCC 4.7315T) should be classified in the genus Streptomyces as Streptomyces qaidamensis sp. nov.
Assuntos
Microbiologia do Solo , Streptomyces/classificação , Streptomyces/genética , China , Genoma Bacteriano , Filogenia , Streptomyces/isolamento & purificação , Streptomyces/ultraestruturaRESUMO
Pest control in agriculture employs diverse strategies, among which the use of predatory insects has steadily increased. The use of several species within the genus Orius in pest control is widely spread, particularly in Mediterranean Europe. Commercial mass rearing of predatory insects is costly, and research efforts have concentrated on diet manipulation and selective breeding to reduce costs and improve efficacy. The characterisation and contribution of microbial symbionts to Orius sp. fitness, behaviour, and potential impact on human health has been neglected. This paper provides the first genome sequence level description of the predominant culturable facultative bacterial symbionts associated with five Orius species (O. laevigatus, O. niger, O. pallidicornis, O. majusculus, and O. albidipennis) from several geographical locations. Two types of symbionts were broadly classified as members of the genera Serratia and Leucobacter, while a third constitutes a new genus within the Erwiniaceae. These symbionts were found to colonise all the insect specimens tested, which evidenced an ancestral symbiotic association between these bacteria and the genus Orius. Pangenome analyses of the Serratia sp. isolates offered clues linking Type VI secretion system effector-immunity proteins from the Tai4 sub-family to the symbiotic lifestyle.
RESUMO
BACKGROUND: As an essential protein for bacterial cell division, the tubulin-like FtsZ protein has been selected as a target for development of next generation antimicrobials. PC190723 is a fluoride-containing benzamide compound developed as a FtsZ inhibitor that selectively inhibits growth of multidrug resistant Gram-positive bacteria. AIM: Our aim was to investigate the mechanism of resistance to PC109723 conferred by over-expression of a gene, rfiA, in an environmental bacterium Arthrobacter A3. MATERIALS & METHODS: The investigations included analysis of the effect of PC109723 on wild-type Arthrobacter A3 and a recombinant strain over-expressing rfiA, in vivo localization of RfiA, in vitro measurements of fluorine release from PC109723 by membrane extracts from the over-expression strain combined with mass spectrophotometric analysis of reaction products, and modelling of RfiA structure. RESULTS: We describe a novel protein, RfiA, from Arthrobacter A3 that confers PC190723 resistance. RfiA is a PAP2 domain-containing polytopic transmembrane protein that can modify the fluoridated benzamide ring that is critical for high affinity binding of PC190723 with FtsZ. CONCLUSION: RfiA-mediated modification of PC190723 is the first reported instance of resistance to this antibiotic involving a change to its structure. We predict that adoption of PC190723 or related benzamides as antimicrobials in clinical practice will lead to the acquisition by resistant pathogens of a gene encoding this subfamily of proteins.
Assuntos
Arthrobacter/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Proteínas do Citoesqueleto/antagonistas & inibidores , Farmacorresistência Bacteriana/genética , Proteínas de Membrana/metabolismo , Piridinas/farmacologia , Tiazóis/farmacologia , Arthrobacter/genética , Arthrobacter/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Benzamidas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/isolamento & purificação , Testes de Sensibilidade Microbiana , FilogeniaRESUMO
Obligate bacterial symbionts are widespread in many invertebrates, where they are often confined to specialized host cells and are transmitted directly from mother to progeny. Increasing numbers of these bacteria are being characterized but questions remain about their population structure and evolution. Here we take a comparative genomics approach to investigate two prominent bacterial symbionts (BFo1 and BFo2) isolated from geographically separated populations of western flower thrips, Frankliniella occidentalis. Our multifaceted approach to classifying these symbionts includes concatenated multilocus sequence analysis (MLSA) phylogenies, ribosomal multilocus sequence typing (rMLST), construction of whole-genome phylogenies, and in-depth genomic comparisons. We showed that the BFo1 genome clusters more closely to species in the genus Erwinia, and is a putative close relative to Erwinia aphidicola. BFo1 is also likely to have shared a common ancestor with Erwinia pyrifoliae/Erwinia amylovora and the nonpathogenic Erwinia tasmaniensis and genetic traits similar to Erwinia billingiae. The BFo1 genome contained virulence factors found in the genus Erwinia but represented a divergent lineage. In contrast, we showed that BFo2 belongs within the Enterobacteriales but does not group closely with any currently known bacterial species. Concatenated MLSA phylogenies indicate that it may have shared a common ancestor to the Erwinia and Pantoea genera, and based on the clustering of rMLST genes, it was most closely related to Pantoea ananatis but represented a divergent lineage. We reconstructed a core genome of a putative common ancestor of Erwinia and Pantoea and compared this with the genomes of BFo bacteria. BFo2 possessed none of the virulence determinants that were omnipresent in the Erwinia and Pantoea genera. Taken together, these data are consistent with BFo2 representing a highly novel species that maybe related to known Pantoea.
Assuntos
Gammaproteobacteria/classificação , Gammaproteobacteria/genética , Genoma Bacteriano , Tisanópteros/microbiologia , Animais , Sistemas de Secreção Bacterianos/genética , Erwinia/classificação , Evolução Molecular , Gammaproteobacteria/isolamento & purificação , Genômica , Filogenia , Simbiose , Fatores de Virulência/genéticaRESUMO
Phylogenetic reconstruction revealed that most Actinobacterial orthologs of S. coelicolor SCO2837, encoding a metal-dependent galactose oxidase-like protein, are found within Streptomyces and were probably acquired by horizontal gene transfer from fungi. Disruption of SCO2837 (glxA) caused a conditional bld phenotype that could not be reversed by extracellular complementation. Studies aimed at characterising the regulation of expression of glxA showed that it is not a target for other bld genes. We provide evidence that glxA is required for osmotic adaptation, although independently from the known osmotic stress response element SigB. glxA has been predicted to be part of an operon with the transcription unit comprising the upstream cslA gene and glxA. However, both phenotypic and expression studies indicate that it is also expressed from an independent promoter region internal to cslA. GlxA displays an in situ localisation pattern similar to that one observed for CslA at hyphal tips, but localisation of the former is independent of the latter. The functional role of GlxA in relation to CslA is discussed.
Assuntos
Galactose Oxidase/genética , Transferência Genética Horizontal , Pressão Osmótica , Streptomyces coelicolor , Actinobacteria/genética , Actinobacteria/metabolismo , Aerobiose/genética , Aerobiose/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Galactose Oxidase/metabolismo , Regulação Bacteriana da Expressão Gênica , Mutação , Osmose , Filogenia , Regiões Promotoras Genéticas , Fator sigma/genética , Fator sigma/metabolismo , Streptomyces coelicolor/genética , Streptomyces coelicolor/metabolismoRESUMO
We report the 4,385,577-bp high-quality draft assembly of the bacterial symbiont Rhodococcus rhodnii strain LMG5362, isolated from the gut of Rhodnius prolixus (Hemiptera, Reduviidae, Triatominae), the principle vector of the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. This sequence might provide useful information for subsequent studies of the symbiotic relationship between Rd. prolixus and Rc. rhodnii, while also providing a starting point for the development of biotechnological applications for the control of Rd. prolixus.
RESUMO
Dps proteins are found almost ubiquitously in bacterial genomes and there is now an appreciation of their multifaceted roles in various stress responses. Previous studies have shown that this family of proteins assemble into dodecamers and their quaternary structure is entirely critical to their function. Moreover, the numbers of dps genes per bacterial genome is variable; even amongst closely related species - however, for many genera this enigma is yet to be satisfactorily explained. We reconstruct the most probable evolutionary history of Dps in Streptomyces genomes. Typically, these bacteria encode for more than one Dps protein. We offer the explanation that variation in the number of dps per genome among closely related Streptomyces can be explained by gene duplication or lateral acquisition, and the former preceded a subsequent shift in expression patterns for one of the resultant paralogs. We show that the genome of S. coelicolor encodes for three Dps proteins including a tailless Dps. Our in vivo observations show that the tailless protein, unlike the other two Dps in S. coelicolor, does not readily oligomerise. Phylogenetic and bioinformatic analyses combined with expression studies indicate that in several Streptomyces species at least one Dps is significantly over-expressed during osmotic shock, but the identity of the ortholog varies. In silico analysis of dps promoter regions coupled with gene expression studies of duplicated dps genes shows that paralogous gene pairs are expressed differentially and this correlates with the presence of a sigB promoter. Lastly, we identify a rare novel clade of Dps and show that a representative of these proteins in S. coelicolor possesses a dodecameric quaternary structure of high stability.
Assuntos
Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Modelos Genéticos , Streptomyces coelicolor/genética , Streptomyces/genética , Sequência de Aminoácidos , Proteínas de Bactérias/classificação , Proteínas de Bactérias/metabolismo , Simulação por Computador , Proteínas de Ligação a DNA/classificação , Proteínas de Ligação a DNA/metabolismo , Evolução Molecular , Duplicação Gênica , Dados de Sequência Molecular , Osmose , Pressão Osmótica , Filogenia , Regiões Promotoras Genéticas , Isoformas de Proteínas/classificação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Multimerização Proteica , Alinhamento de Sequência , Streptomyces/classificação , Streptomyces/metabolismo , Streptomyces coelicolor/metabolismoRESUMO
The DpsA protein plays a dual role in Streptomyces coelicolor, both as part of the stress response and contributing to nucleoid condensation during sporulation. Promoter mapping experiments indicated that dpsA is transcribed from a single, sigB-like dependent promoter. Expression studies implicate SigH and SigB as the sigma factors responsible for dpsA expression while the contribution of other SigB-like factors is indirect by means of controlling sigH expression. The promoter is massively induced in response to osmotic stress, in part due to its sensitivity to changes in DNA supercoiling. In addition, we determined that WhiB is required for dpsA expression, particularly during development. Gel retardation experiments revealed direct interaction between apoWhiB and the dpsA promoter region, providing the first evidence for a direct WhiB target in S. coelicolor.