Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Global metabolic response of Enterococcus faecalis to oxygen.

ABSTRACT: Oxygen and oxidative stress have become relevant components in clarifying the mechanism that weakens bacterial cells in parallel to the mode of action of bactericidal antibiotics. Given the importance of oxidative stress in the overall defense mechanism of bacteria and their apparent role in the antimicrobial mode of action, it is important to understand how bacteria respond to this stress at a metabolic level. The aim of this study was to determine the impact of oxygen on the metabolism of the facultative anaerobe Enterococcus faecalis using continuous culture, metabolomics, and (13)C enrichment of metabolic intermediates. When E. faecalis was rapidly transitioned from anaerobic to aerobic growth, cellular metabolism was directed toward intracellular glutathione production and glycolysis was upregulated 2-fold, which increased the supply of critical metabolite precursors (e.g., glycine and glutamate) for sulfur metabolism and glutathione biosynthesis as well as reducing power for cellular respiration in the presence of hemin. The ultimate metabolic response of E. faecalis to an aerobic environment was the upregulation of fatty acid metabolism and benzoate degradation, which was linked to important changes in the bacterial membrane composition as evidenced by changes in membrane fatty acid composition and the reduction of membrane-associated demethylmenaquinone. These key metabolic pathways associated with the response of E. faecalis to oxygen may represent potential new targets to increase the susceptibility of this bacterium to bactericidal drugs.

SUBMITTER: Portela CA

PROVIDER: S-EPMC4010974 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Global transcriptional analysis of the stringent response in Enterococcus faecalis.

Project description:In Enterococcus faecalis, production of guanosine tetraphosphate/guanosine pentaphosphate [(p)ppGpp], the effector molecule of the stringent response, is controlled by the bifunctional synthetase/hydrolase RelA and the monofunctional synthetase RelQ. Previously, the (p)ppGpp profiles of strains lacking relA, relQ or both genes indicated that RelA is the primary enzyme responsible for (p)ppGpp synthesis under stress conditions, while the contributions of RelQ to the stringent response and cell homeostasis remained elusive. Here, survival within the mouse-derived macrophage cell line J774A.1 and killing of Galleria mellonella supported initial evidence that virulence was attenuated in the (p)ppGpp(0) ?relA?relQ strain but not in the ?relA or ?relQ strains. We performed, for the first time to our knowledge, global transcriptome analysis in a documented (p)ppGpp(0) Gram-positive bacterium and provided the first insights into the role of a Gram-positive monofunctional (p)ppGpp synthetase in transcriptional regulation. Transcription profiling after mupirocin treatment confirmed that RelA is the major enzyme responsible for the (p)ppGpp-mediated transcriptional repression of genes associated with macromolecular biosynthesis, but also revealed that RelQ is required for full and timely stringent response induction. The delayed transcriptional response of ?relQ could not be correlated with reduced or slower production of (p)ppGpp, in part because RelA-dependent (p)ppGpp accumulation occurred very rapidly. Comparisons of the transcriptional responses of ?relA or ?relA?relQ strains with the parent strain under starvation conditions revealed upregulation of operons involved in energy metabolism in the (p)ppGpp(0) strain. Thus, while ?relA and ?relA?relQ cannot use (p)ppGpp to sense and respond to stresses, fitness of ?relA?relQ may be further impaired due to an unbalanced metabolism.

| S-EPMC4811642 | biostudies-literature

Transcriptional activation by MafR, a global regulator of Enterococcus faecalis.

Project description:Proteins that act as global transcriptional regulators play key roles in bacterial adaptation to new niches. These proteins recognize multiple DNA sites across the bacterial genome by different mechanisms. Enterococcus faecalis is able to survive in various niches of the human host, either as a commensal or as a leading cause of serious infections. Nonetheless, the regulatory pathways involved in its adaptive responses remain poorly understood. We reported previously that the MafR protein of E. faecalis causes genome-wide changes in the transcriptome. Here we demonstrate that MafR functions as a transcription activator. In vivo, MafR increased the activity of the P12294 and P11486 promoters and also the transcription levels of the two genes controlled by those promoters. These genes are predicted to encode a calcium-transporting P-type ATPase and a QueT transporter family protein, respectively. Thus, MafR could have a regulatory role in calcium homeostasis and queuosine synthesis. Furthermore, MafR recognized in vitro specific DNA sites that overlap the -35 element of each target promoter. The MafR binding sites exhibit a low sequence identity, suggesting that MafR uses a shape readout mechanism to achieve DNA-binding specificity.

| S-EPMC6467988 | biostudies-literature

Global transcriptional response to copper of Enterococcus faecalis wild-type and copY mutant

Project description:We examined the whole-genome transcriptional response of E. faecalis wild-type (WT) and copy mutant cells exposed to non toxic Cu excess. The analysis was focused in those genes which changed significantly their expression levels in the Cu-treated cells when compared to their untreated counterparts. The results indicated that after 3 h at 0.5 mM CuSO4, WT cells exhibited a significant increment of Cu content and the induction of three genes of cop operon along with other 142 genes. The comparison with the copY mutant exposed to Cu showed an extensive overlapping of transcriptional changes suggesting that other transcription factors may be mediating the response to Cu. Associated manuscript The global response of Enterococcus faecalis to copper exposure

2011-02-14 | GSE20453 | GEO

DNA-binding properties of MafR, a global regulator of Enterococcus faecalis.

Project description:Global transcriptional regulators play key roles during bacterial adaptation to environmental fluctuations. Protein MafR from Enterococcus faecalis was shown to activate the transcription of many genes on a genome-wide scale. We proposed that MafR is a global regulator of the Mga/AtxA family. Here, we purified an untagged form of the MafR protein and found that it binds to linear double-stranded DNAs in a nonsequence-specific manner. Moreover, multiple MafR units (likely dimers) bind sequentially to the DNA molecule generating multimeric complexes. On DNAs that contain the promoter of the mafR gene, MafR recognizes a potentially curved DNA region. We discuss that a characteristic of the Mga/AtxA regulators might be their ability to recognize particular DNA shapes across the bacterial genomes.

| S-EPMC5947639 | biostudies-literature

Transcriptomic response of Enterococcus faecalis to iron excess

Project description:To further investigate the homeostatic response of E. faecalis to Fe exposure, we examine the whole-genome transcriptional response of wild-type (WT) exposed to non toxic Fe excess. This experiment correspond the work titled Transcriptomic response of Enterococcus faecalis to iron excess (work in preparation)

2012-03-01 | GSE34432 | GEO

Global Regulation of Gene Expression by the MafR Protein of Enterococcus faecalis.

Project description:Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. However, as an opportunistic pathogen, it is able to colonize other host niches and cause life-threatening infections. Its adaptation to new environments involves global changes in gene expression. The EF3013 gene (here named mafR) of E. faecalis strain V583 encodes a protein (MafR, 482 residues) that has sequence similarity to global response regulators of the Mga/AtxA family. The enterococcal OG1RF genome also encodes the MafR protein (gene OG1RF_12293). In this work, we have identified the promoter of the mafR gene using several in vivo approaches. Moreover, we show that MafR influences positively the transcription of many genes on a genome-wide scale. The most significant target genes encode components of PTS-type membrane transporters, components of ABC-type membrane transporters, and proteins involved in the metabolism of carbon sources. Some of these genes were previously reported to be up-regulated during the growth of E. faecalis in blood and/or in human urine. Furthermore, we show that a mafR deletion mutant strain induces a significant lower degree of inflammation in the peritoneal cavity of mice, suggesting that enterococcal cells deficient in MafR are less virulent. Our work indicates that MafR is a global transcriptional regulator. It might facilitate the adaptation of E. faecalis to particular host niches and, therefore, contribute to its potential virulence.

| S-EPMC4707282 | biostudies-literature

Transcriptome analysis of Enterococcus faecalis in response to alkaline stress.

Project description:Enterococcus faecalis is the most commonly isolated species from endodontic failure root canals; its persistence in treated root canals has been attributed to its ability to resist high pH stress. The goal of this study was to characterize the E. faecalis transcriptome and to identify candidate genes for response and resistance to alkaline stress using Illumina HiSeq 2000 sequencing. We found that E. faecalis could survive and form biofilms in a pH 10 environment and that alkaline stress had a great impact on the transcription of many genes in the E. faecalis genome. The transcriptome sequencing results revealed that 613 genes were differentially expressed (DEGs) for E. faecalis grown in pH 10 medium; 211 genes were found to be differentially up-regulated and 402 genes differentially down-regulated. Many of the down-regulated genes found are involved in cell energy production and metabolism and carbohydrate and amino acid metabolism, and the up-regulated genes are mostly related to nucleotide transport and metabolism. The results presented here reveal that cultivation of E. faecalis in alkaline stress has a profound impact on its transcriptome. The observed regulation of genes and pathways revealed that E. faecalis reduced its carbohydrate and amino acid metabolism and increased nucleotide synthesis to adapt and grow in alkaline stress. A number of the regulated genes may be useful candidates for the development of new therapeutic approaches for the treatment of E. faecalis infections.

| S-EPMC4528170 | biostudies-literature

Transcriptome mapping of Enterococcus faecalis and Enterococcus faecium

Project description:The enterococci comprise a genus of 49 low-GC content Gram-positive commensal species within the Firmicutes phylum that are known to occupy diverse habitats, notably the gastrointestinal core microbiota of nearly every phylum, including human. Of particular clinical relevance are two rogue species of enterococci, Enterococcus faecalis and the distantly related Enterococcus faecium, standing among the nefarious multi-drug resistant and hospital-acquired pathogens. Despite increasing evidence for RNA-based regulation in the enterococci, including regulation of virulence factors, their transcriptome structure and arsenal of regulatory small sRNAs (sRNAs) are not thoroughly understood. Using dRNA-seq, we have mapped at single-nucleotide resolution the primary transcriptomes of E. faecalis V583 and E. faecium AUS0004. We identified 2517 and 2771 transcription start sites (TSS) in E. faecalis and E. faecium, respectively. Based on the identified TSS, we created a global map of s70 promoter motifs. We also revealed features of 5’ and 3’UTRs across the genomes. The transcriptome maps also predicted 150 and 128 sRNA candidates in E. faecalis and E. faecium, respectively, some of which have been identified in previous studies and many of which are new. Finally, we validated several of the predicted sRNAs by Northern Blot in biologically relevant conditions. Comprehensive TSS mapping of two representative strains will provide a valuable resource for the continued development of RNA biology in the Enterococci.

2020-11-25 | GSE115009 | GEO

Involvement of Enterococcus faecalis small RNAs in stress response and virulence.

Project description:Candidate small RNAs (sRNAs) have recently been identified in Enterococcus faecalis, a Gram-positive opportunistic pathogen, and six of these candidate sRNAs with unknown functions were selected for a functional study. Deletion mutants and complemented strains were constructed, and their virulence was tested. We were unable to obtain the ef0869-0870 mutant, likely due to an essential role, and the ef0820-0821 sRNA seemed not to be involved in virulence. In contrast, the mutant lacking ef0408-0409 sRNA, homologous to the RNAII component of the toxin-antitoxin system, appeared more virulent and more able to colonize mouse organs. The three other mutants showed reduced virulence. In addition, we checked the responses of these mutant strains to several stresses encountered in the gastrointestinal tract or during the infection process. In parallel, the activities of the sRNA promoters were measured using transcriptional fusion constructions. To attempt to identify the regulons of these candidate sRNAs, proteomics profiles of the mutant strains were compared with that of the wild type. This showed that the selected sRNAs controlled the expression of proteins involved in diverse cellular processes and the stress response. The combined data highlight the roles of certain candidate sRNAs in the adaptation of E. faecalis to environmental changes and in the complex transition process from a commensal to a pathogen.

| S-EPMC4187846 | biostudies-other

Genetic diversity among Enterococcus faecalis.

Project description:Enterococcus faecalis, a ubiquitous member of mammalian gastrointestinal flora, is a leading cause of nosocomial infections and a growing public health concern. The enterococci responsible for these infections are often resistant to multiple antibiotics and have become notorious for their ability to acquire and disseminate antibiotic resistances. In the current study, we examined genetic relationships among 106 strains of E. faecalis isolated over the past 100 years, including strains identified for their diversity and used historically for serotyping, strains that have been adapted for laboratory use, and isolates from previously described E. faecalis infection outbreaks. This collection also includes isolates first characterized as having novel plasmids, virulence traits, antibiotic resistances, and pathogenicity island (PAI) components. We evaluated variation in factors contributing to pathogenicity, including toxin production, antibiotic resistance, polymorphism in the capsule (cps) operon, pathogenicity island (PAI) gene content, and other accessory factors. This information was correlated with multi-locus sequence typing (MLST) data, which was used to define genetic lineages. Our findings show that virulence and antibiotic resistance traits can be found within many diverse lineages of E. faecalis. However, lineages have emerged that have caused infection outbreaks globally, in which several new antibiotic resistances have entered the species, and in which virulence traits have converged. Comparing genomic hybridization profiles, using a microarray, of strains identified by MLST as spanning the diversity of the species, allowed us to identify the core E. faecalis genome as consisting of an estimated 2057 unique genes.

| S-EPMC1899230 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data