C-di-AMP signaling is required for bile salts resistance and long-term colonization by Clostridioides difficile
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA791846 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17319807.fastq.gz | Fastqsanger.gz | |||
| SRR17319808.fastq.gz | Fastqsanger.gz | |||
| SRR17319809.fastq.gz | Fastqsanger.gz | |||
| SRR17319810.fastq.gz | Fastqsanger.gz | |||
| SRR17319811.fastq.gz | Fastqsanger.gz |
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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:The obligate intracellular bacterium Chlamydia alternates between two functional forms during its developmental cycle: elementary body (EB) and reticulate body (RB). However, the molecular mechanisms governing the transitions between these forms are unknown. Here, we present evidence cyclic di-AMP (c-di-AMP) is a key factor in triggering the transition from RB to EB (i.e., secondary differentiation) in the chlamydial developmental cycle. We made strains producing different levels of c-di-AMP, which we linked to changes in secondary differentiation status. Increases in c-di-AMP resulted in an earlier increase in transcription of EB-associated genes, and this was further manifested in earlier production of EBs. In contrast, when c-di-AMP levels were decreased, secondary differentiation was delayed. Based on these data, we conclude there is a threshold level of c-di-AMP needed to trigger secondary differentiation in Chlamydia. This is the first study to define a mechanism of secondary differentiation in Chlamydia.
2025-08-21 | GSE252732 | GEO
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: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:This experiment is to investigate E.faecium E1162 transcriptome profiles under bile salts activation.
2013-10-10 | E-MEXP-3796 | biostudies-arrayexpress
Project description:A genome-wide identification of the genetic loci required for bile salts resistance in E. faecium
2013-10-10 | E-MEXP-3797 | biostudies-arrayexpress
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:Few are the studies that analyzed the molecular features implicated to the tolerance to bile salts by A.baumannii clinical strains. Interestingly, Ab421 GEIH-2010 strain (belonging to ST79/PFGE-HUI-1 clone constitute by isolates with lacking of the AdeABC efflux pump) and A.baumannii ∆adeB ATCC 17978 showed higher tolerance to bile salts by the expression of the glutamate/aspartate transporter as well as virulence factors (Type VI Secretion System, twitching motility and biofilm) associated to the activation of the Quorum Sensing system.
2017-06-09 | GSE85264 | GEO
Project description:Purpose：Bifidobacteria are common inhabitants of the human gastrointestinal tract. In order to colonize in the gut, it is important to adapt to the physiological concentrations of bile salts. The global response to bile in B. longum BBMN68, isolated from a healthy centenarian in the Bama County of the Guangxi Zhuang Autonomous Region in China, has been investigated through RNA-seq transcriptomics sequencing in our previous work. However, a long-term bile salts treatment is more suitable to simulate the human gastrointestinal tract environment. The goals of this study are to invstigated the global response to a long-term treatment of bile salts in B. longum BBMN68. Methods: Samples from BBMN68 cultured with or without 0.75 g liter-1 ox-bile for 24 hours were sequenced on an Illumina Hiseq platform. Three independent biological replicates were produced including 6 samples in total. Results: Raw data were firstly processed through in-house perl scripts to generate clean data, and then clean date were mapped to the reference genome, getting about 11-13 million total mapped reads per sample.
2018-05-04 | GSE113993 | 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