σE of Streptomyces coelicolor can function both as a direct activator or repressor of transcription

Pospíšil, Jiří; Schwarz, Marek; Ziková, Alice; Vítovská, Dragana; Hradilová, Miluše; Kolář, Michal; Křenková, Alena; Hubálek, Martin; Krásný, Libor; Vohradský, Jiří

doi:10.1038/s42003-023-05716-y

Cited by 3 publications

(1 citation statement)

References 78 publications

(129 reference statements)

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“…Similarly, a two-component response system encoded by genes immediately upstream of RS22785 and transcribed in opposite direction may also control the latter ECF. The ECF σ E , a major regulator of cell envelope stress in S. coelicolor , is controlled by a two-component system [ 44 ], and it might be tempting to assume that ECFs responding to ethanol shock could play a similar role. However, this remains an open question, since no appreciable homology (< 30%) could be found between the amino acid sequences of σ E and the three ECFs characterized in this study.…”

Section: Discussionmentioning

confidence: 99%

Deletions of conserved extracytoplasmic function sigma factors-encoding genes in Streptomyces have a major impact on secondary metabolism

Sekurova,

Zehl,

Predl

et al. 2024

Microb Cell Fact

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Background Ethanol shock significantly affects expression of over 1200 genes in Streptomyces venezuelae NRRL B-65,442, including those involved in secondary metabolite biosynthesis and a cryptic gene pepX, which encodes a 19-amino acid peptide with an unknown function. Results To establish a possible correlation between the PepX peptide and secondary metabolism in S. venezuelae, its gene was deleted, followed by analyses of the transcriptome and secondary metabolome of the mutant. Although the secondary metabolome of the pepX mutant was not strongly affected, pepX deletion, similar to ethanol shock, mostly resulted in downregulated expression of secondary metabolite biosynthesis gene clusters (BGCs). At the same time, there was a reverse correlation between the expression of certain extracytoplasmic function sigma factors (ECFs) and several BGCs. Individual deletions of three selected ECF-coding genes conserved in Streptomyces that were upregulated upon both pepX deletion and ethanol shock, had a profound positive effect on the expression of BGCs, which also correlated with the overproduction of specific secondary metabolites. Deletion of one such ECF-coding gene in a marine sponge-derived Streptomyces sp. also significantly altered the secondary metabolite profile, suggesting an important role of this ECF in the regulation of secondary metabolism. Conclusions These findings pave the way for the activation or upregulation of BGCs in Streptomyces bacteria harboring genes for ECFs homologous to those identified in this study, hereby assisting in the discovery of novel bioactive secondary metabolites.

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Section: Discussionmentioning

confidence: 99%

Deletions of conserved extracytoplasmic function sigma factors-encoding genes in Streptomyces have a major impact on secondary metabolism

Sekurova,

Zehl,

Predl

et al. 2024

Microb Cell Fact

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Secondary metabolites shapeStreptomyces-Streptomycesinteraction: Mass Spectrometry Imaging reveals lydicamycins broadly induce sporulation

Jarmusch,

Schostag,

Yang

et al. 2024

Preprint

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Streptomycesare major players in soil microbiomes, however, interactions involvingStreptomyces-Streptomycesare rarely described. The complex developmental cycle of Streptomycetes necessitates a multi-omics approach to unravel the web of information. This study resulted from the observation of induced sporulation between two environmental isolates from the same site,Streptomycessp. P9-2B1 andStreptomycessp. P9-2B2. When co- cultivated on potato dextrose agar (PDA), P9-2B2 induced a wave-like sporulation in strain P9- 2B1. Using Mass Spectrometry Imaging, we revealed that a suite of lydicamycins, antibacterial NRPS-PKS hybrid metabolites, were present in this induced sporulation zone. Lydicamycin deficient mutants were generated using CRISPR-base editing and the inducible sporulation ceased, confirming their role in triggering morphological differentiation. In agar diffusion assays, pure lydicamycin was inhibitory when added concurrently with bacterial inoculation and induced sporulation with delayed addition. Subsequent testing of additional environmental isolates resulted in the same inducible sporulation wave phenomenon, includingStreptomyces coelicolorM145 and M1146. We further evaluated the temporal production of the lydicamycins in monoculture over a 10-day time scale. On PDA, production was detectable upon sporulation at day 4 on PDA and peaked at day 9. On ISP2, lydicamycin production was minimal and stable over the 10 days, coinciding with a lack of sporulation. Using transcriptomics, we observed the upregulation of early aerial mycelium development related genes four days into cocultivation and also the transitional genes responsible for development of spores on day 9. Along with these upregulated genes, we also observed numerous overall stress responses, specifically cell envelope stress responses. This finding uncoveredStreptomyces-Streptomycesinteractions mediated by lydicamycins, pointing to a potential role of certain groups of bioactive metabolites in nature.

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The role of two major nucleoid-associated proteins in Streptomyces, HupA and HupS, in stress survival and gene expression regulation

Strzałka,

Mikołajczyk,

Kowalska

et al. 2024

Microb Cell Fact

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Background Streptomyces are sporulating soil bacteria with enormous potential for secondary metabolites biosynthesis. Regulatory networks governing Streptomyces coelicolor differentiation and secondary metabolites production are complex and composed of numerous regulatory proteins ranging from specific transcriptional regulators to sigma factors. Nucleoid-associated proteins (NAPs) are also believed to contribute to regulation of gene expression. Upon DNA binding, these proteins impact DNA accessibility. Among NAPs, HU proteins are the most widespread and abundant. Unlike other bacteria, the Streptomyces genomes encode two HU homologs: HupA and HupS, which differ in structure and expression profile. However, it remained unclear whether the functions of both homologs overlap. Additionally, although both proteins have been shown to bind the chromosome, their rolesin transcriptional regulation have not been studied so far. Results In this study, we explore whether HupA and HupS affect S. coelicolor growth under optimal and stressful conditions and how they control global gene expression. By testing both single and double mutants, we address the question of the complementarity of both HU homologs. We show that the lack of both hup genes led to growth and sporulation inhibition, as well as increased spore fragility. We also demonstrate that both HU homologs can be considered global transcriptional regulators, influencing expression of between 2% and 6% genes encoding among others proteins linked to global regulatory networks and secondary metabolite production. Conclusions We identify the independent HupA and HupS regulons, as well as genes under the control of both HupA and HupS proteins. Our data indicate a partial overlap between the functions of HupA and HupS during S. coelicolor growth. HupA and HupS play important roles in Streptomyces regulatory network and impact secondary metabolite clusters.

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σE of Streptomyces coelicolor can function both as a direct activator or repressor of transcription

Cited by 3 publications

References 78 publications

Deletions of conserved extracytoplasmic function sigma factors-encoding genes in Streptomyces have a major impact on secondary metabolism

Deletions of conserved extracytoplasmic function sigma factors-encoding genes in Streptomyces have a major impact on secondary metabolism

Secondary metabolites shapeStreptomyces-Streptomycesinteraction: Mass Spectrometry Imaging reveals lydicamycins broadly induce sporulation

The role of two major nucleoid-associated proteins in Streptomyces, HupA and HupS, in stress survival and gene expression regulation

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