A network of acetyl phosphate-dependent modification supports c-di-AMP homeostasis in Actinobacteria
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1000917 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25474256_1.fastq.gz | Fastqsanger.gz | |||
| SRR25474256_2.fastq.gz | Fastqsanger.gz | |||
| SRR25474257_1.fastq.gz | Fastqsanger.gz | |||
| SRR25474257_2.fastq.gz | Fastqsanger.gz | |||
| SRR25474258_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:C-di-AMP is primarily associated with the regulation of carbon utilization as well as other central traits, central metabolism, and bacterial stringent response to environmental changes. Elevated c-di-AMP levels result in aberrant physiology for most c-di-AMP synthesizing organisms, drawing particular attention to the importance of the c-di-AMP homeostasis and the molecular mechanisms pertaining to nucleotide metabolism and signal transduction. Here we show that c-di-AMP binds the GntR-family regulator DasR, uncovering a direct link between c-di-AMP and GlcNAc signaling. Further, we show c-di-AMP functions as an allosteric activator of DasR activity. GlcNAc is necessary for cell-surface structure from bacteria to humans, as well as a signal for bacterial development and antibiotic production. DasR is a global repressor that oversees GlcNAc metabolism and antibiotic production, which enables Actinobacteria to cope with stress and starvation. Our in vivo studies reveal the important biological role of allosteric regulation by c-di-AMP in metabolic imbalance and the transduction of a series of signals. Notably, DasR also controls intracellular c-di-AMP level through direct repression on disA. Overall, we identify a function of allosteric regulation between c-di-AMP and DasR in global signal integration and c-di-AMP homeostasis in bacteria, which is likely widespread in Actinobacteria.
2024-03-31 | GSE229938 | GEO
Project description:K78 acetylation inhibits the global outcome of DasR binding to its targeted genes in vivo.
2024-06-27 | GSE239753 | GEO
Project description:Allosteric regulation by c-di-AMP modulates global signal integration in Actinobacteria
| PRJNA956843 | ENA
Project description:Streptococcus pneumoniae harbors two cyclic di-AMP (c-di-AMP) phosphodiesterases Pde1 and Pde2. Previously, we demonstrated that deletion of one or both of these proteins leads to growth retardation in culture media, defects in the bacterial stress response, and attenuation in mouse models of disease. All of these phenotypes are due to increased levels of c-di-AMP, since the nature and break down products of each protein are different, and mutations that lower c-di-AMP levels partially restore growth and stress tolerance in these mutants. However, how c-di-AMP mediates pneumococcal stress resistance and virulence is unknown. To establish how c-di-AMP affects the transcriptome, RNA-Seq analysis was employed to compare gene expression between wild-type and Δpde1Δpde2 (ST2734) pneumococci. Overall, the competence regulon was upregulated in the Δpde1Δpde2 mutant.
2018-04-18 | GSE113231 | GEO
Project description:Actinobacteria are ubiquitous bacteria undergoing complex developmental transition coincided with antibiotics production in response to stress or nutrients starvation. This transition is mainly controlled by the interaction between the second messenger c-di-GMP and the master repressor BldD. To date, the upstream factors and the global signal networks that regulate this intriguing cell biological processes still remained unknown. In Saccharopolyspora erythraea, we found that acetyl phosphate (AcP) accumulation resulting from environmental nitrogen stress participated in the regulation of BldD activity through cooperation with c-di-GMP. AcP-induced acetylation of BldD at K11 caused the BldD dimer to fall apart and dissociate from the target DNA, as well as disrupted the signal transduction of c-di-GMP, thus governed both developmental transition and antibiotics production. Meanwhile, practical mutation of BldDK11R bypassing the acetylation regulation could enhance the positive effect of BldD on antibiotics production. Our finding represents an entirely different role of the covalent modification caused by AcP, which integrated with c-di-GMP signal in modulating the activity of BldD for development and antibiotic production coping with environmental stress. This coherent and highly conserved regulatory network might offer new insight into the direct connections from specific regulator to the actinobacteria biological process associated with major morphogenetic event
2023-08-08 | GSE225241 | GEO
Project description:Cyclic di-AMP is an essential second messenger in many Gram-positive bacteria, including the model organism Bacillus subtilis. Here, we analyzed the transcriptome of a strain accumulating c-di-AMP in vivo. Our results demonstrate that accumulation of c-di-AMP affects the expression of several hundred genes, among them many mother-cell specific sporulation genes. Additionally, the two major biofilm operons, epsA-O and tapA-sipW-tasA, are affected. High levels of c-di-AMP abolish transcription of genes responsible for biofilm formation which in turn leads to a defect in complex colony formation in B. subtilis.
2016-05-25 | GSE79716 | GEO
Project description:Second messenger nucleotides such as c-di-AMP are produced by bacteria in response to environmental stimuli and can contribute to the regulation of a number of cellular processes including osmoregulation, envelope homeostasis, central metabolism, and biofilm formation. Here, as part of an effort to uncover the biological significance of c-di-AMP in the opportunistic pathogen Enterococcus faecalis, we utilized high-throughout RNA Sequencing analysis to explore the impact of deletion of genes responsible for c-di-AMP synthesis (cdaA) and degradation (dhhP and gdpP).
2021-05-14 | GSE174381 | GEO
Project description:In this study, we showed for the first time that c-di-AMP is produced by C. difficile and controls the uptake of potassium, making it essential for growth. We found that c-di-AMP is involved in biofilm formation, cell wall homeostasis, osmotolerance as well as detergent and bile salt resistance in C. difficile. We identified BusR as a new regulator that binds c-di-AMP and represses the expression of the compatible solute transporter BusAA-AB. Interestingly, a busR mutant is highly resistant to a hyperosmotic or bile salt stress compared to the parental strain while a busAA mutant is more susceptible. A short exposure of C. difficile cells to bile salts resulted in a decrease of the c-di-AMP concentrations reinforcing the hypothesis that changes in membrane characteristics due to variations of the cellular turgor or membrane damages constitute a signal for the adjustment of the intracellular c-di-AMP concentration. In a colonization mouse model, a strain producing elevated c-di-AMP concentrations failed to persist in the gut in contrast to the parental strain. Thus, c-di-AMP is a signaling molecule with pleiotropic effects that controls osmolyte uptake to confer osmotolerance and bile salt resistance in C. difficile and that is important for colonization of the host.
2021-12-27 | GSE192529 | GEO
Project description:c-di-GMP and c-di-AMP are important conserved second messenger in bacteria, they play a critical role in a wide range of cellular processes, such as motility, virulence, biofilm formation, cell-cycle progression and cell development, but there are only two c-di-GMP receptors and one c-di-AMP receptors were identified in mycobacteria so far, to identify more c-di-GMP and c-di-AMP receptors we compare the protein expression level of c-di-GMP or c-di-AMP synthesis enzyme overexpression strain with the wild type Mycobacterium smegmatis.
2019-07-03 | PXD010623 | Pride
Project description:The bacterial second messenger c-di-AMP controls various cellular processes including potassium and osmolyte homeostasis. The c-di-AMP receptor protein DarB of Bacillus subtilis binds to the Rel protein and triggers the Rel-dependent stringent response. Here we report crystal structures of DarB in the ligand-free state and of DarB complexes with c-di-AMP, 3´3´-cGAMP and AMP. DarB consists of two CBS domains and forms a homo-dimer with a parallel, head-to-head assembly of the monomers. The DarB dimer binds two cyclic di-nucleotide molecules or two AMP molecules. Only one adenine of bound c-di-AMP is specifically recognized by DarB, while the second one protrudes out of the donut-shaped protein. This enables DarB to bind also 3´3´-cGAMP, as only the adenine fits to the active site, but not the guanine. In absence of c-di-AMP DarB binds to Rel and stimulates (p)ppGpp synthesis, whereas the presence of c-di-AMP abolishes the interaction. The DarB crystal structures reveal no conformational changes upon c-di-AMP binding, hence, the regulatory function of DarB on Rel must be controlled directly by the bound c-di-AMP. A structural model of the DarB-Rel complex was erived from in silico docking, validated with a mass spectrometric analysis of the chemically cross-linked DarB-Rel complex and mutagenesis studies. Based on the predicted complex structure a mechanism of stringent response regulation by c-di-AMP is suggested.
2022-08-12 | PXD033346 | Pride