Characterization of Staphylococcus epidermidis biofilm-released cells (BRC) transcriptome upon interaction with whole human blood and its cellular and soluble components
Ontology highlight
ABSTRACT:
ORGANISM(S): Staphylococcus epidermidis
PROVIDER: GSE79948 | GEO | 2017/02/10
SECONDARY ACCESSION(S): PRJNA317500
REPOSITORIES: GEO
Similar Datasets
Project description:S. epidermidis ability to form biofilms on indwelling medical devices and its association with the emergence of chronic infections is its main virulence factor. Nevertheless, it has been shown that the cells released from these biofilms are associated with the advent of serious acute infections with bacteraemia as one of the major clinical manifestations. Despite their clinical relevance, very little is known about the impact of biofilm-released cells in pathogenesis. Hence, herein, we characterized the murine immune response to the presence of cells released from S. epidermidis biofilms analysing spleen cells transcriptome by microarrays. These findings may help to explain the recurrent inflammatory symptoms presented by patients with colonization of indwelling medical devices.
2017-02-22 | GSE60992 | GEO
Project description:The release of cells from S. epidermidis biofilms formed on medical devices has been associated with the onset of bloodstream infections, resulting in increased morbidity and mortality rates. This has to do, in part, with the difficulty to accurately diagnose S. epidermidis bloodstream infections. S. epidermidis is a ubiquitous commensal of human skin and mucosa and, thus, a positive blood culture does not always represent an infection, possibly being the result of contamination during blood collection. As such, there is a high demand to find markers that can help clinicians to distinguish infection (clinical isolates) from contamination (commensal strains). With that in mind, several studies comparing phenotypic or genetic characteristics of clinical and commensal isolates have been performed over the years. However, because S. epidermidis virulence factors seem to be the same that confer its fitness as a commensal, we hypothesized that the ability of S. epidermidis strains to adapt to the host environment may not depend on a specific phenotypic and/or genetic makeup, but rather on the regulation of gene transcription. Thus, using RNA-Sequencing (RNA-seq), we characterized the transcriptome of commensal and clinical isolates in the context of infection to try to uncover differences and, thus, identify markers that could be used for the diagnostics. Several markers with the potential to discriminate between both groups were highlighted. Nevertheless, when the results obtained were confirmed in a wider collection of clinical and commensal isolates the discriminatory power of the genes initially identified was lost. Although we cannot rule out that the characterization of a larger collection of isolates would identify potential candidates, our transcriptomic data was not able to confirm our initial hypothesis, evidencing S. epidermidis opportunistic nature.
2022-12-09 | GSE179407 | GEO
Project description:Staphylococcus epidermidis is a common causative of nosocomial infections associated with indwelling medical devices. To date, the mechanisms of the pathogenicity and drug resistance of S. epidermidis have not been clearly elucidated. AbfR has been previously identified as an oxidation-sensing regulator that regulates bacterial aggregation and biofilm formation by responding to oxidative stress in S. epidermidis; however, the regulatory pathways of AbfR are underexplored. In this study, we investigated the oxidation-sensing regulatory mechanism of AbfR using TMT10-plex labelling quantitative proteomic and untargeted metabolomic approaches. Integrated analysis of two omics datasets indicated that abfR depletion influenced nucleic acid metabolism and activated the DNA mismatch repair pathway. In addition, several energy-related metabolic pathways, including tricarboxylic acid (TCA) cycle, glycolysis, and arginine metabolism, were remarkably impacted by the deletion of abfR. This study revealed the regulatory networks of the transcription factor AbfR from a multi-omics view and demonstrated that AbfR played a broad role in not only mismatch repair but also energy metabolism, enabling S. epidermidis to constantly sense and adapt to environmental stress.
2020-07-29 | PXD020096 | Pride
Project description:To investigate the effect of synthetic phenol-soluble modulins (PSMs) secreted by S. epidermidis on primary keratinocytes. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cells at two time points.
2023-01-01 | GSE209653 | GEO
Project description:Staphylococcus epidermidis (SE) is one of the most common bacteria of the human skin microbiota. Despite its role as a commensal, SE has emerged as an opportunistic pathogen, associated with 80% of medical devices related infections. Moreover, these bacteria are extremely difficult to treat due to their ability to form biofilms and accumulate resistance to almost all classes of antimicrobials developed so far. Thus new preventive and therapeutic strategies are urgently needed. In spite of its clinical importance, the molecular mechanisms associated with SE colonisation and disease are still poorly understood. A deeper understanding of the metabolic and cellular processes associated with response to environmental factors characteristic of SE ecological niches in health and disease might provide new clues on colonisation and disease processes. Here we studied the impact of pH conditions, mimicking the skin pH (5.5) and blood pH (7.4), in a S. epidermidis commensal strain, belonging to the B clonal lineage, by means of next-generation proteomics and 1H NMR-based metabolomics. Moreover, we evaluated the metabolic changes occurring when a sudden pH change arise, simulating the skin barrier break produced by a catheter. We found that exposure of S. epidermidis to skin pH induced oxidative phosphorylation and biosynthesis of peptidoglycan, lipoteichoic acids and betaine. In contrast, at blood pH, the incorporation of monosaccharides and its oxidation by glycolysis and fermentation was promoted. Additionally, several proteins related to virulence and immune evasion, namely extracellular proteases and membrane iron transporters were more abundant at blood pH. In the situation of an abrupt skin-to-blood pH shift we observed the decrease in the osmolyte betaine and changes in the levels of several metabolites and proteins involved in redox cell homeostasis. Our results suggest that at the skin pH S. epidermidis cells are metabolically more active and adhesion is promoted, while at blood pH, metabolism is tuned down and cells have a more virulent profile. pH increase during commensal-to-pathogen conversion appears to be a critical environmental signal to the remodelling of the S. epidermidis metabolism towards a more pathogenic state. Targeting S. epidermidis proteins induced by a low alkaline pH and local acidification of medical devices microenvironment might be new strategies to treat and prevent S. epidermidis infections.
2022-07-14 | ST002277 | MetabolomicsWorkbench
Project description:To investigate the effect of both S. epidermidis phenol-soluble modulins (PSMs) and EcpA genetic knockouts on murine back skin. We then performed gene expression profiling analysis using data obtained from RNA-seq of 5 conditions (n=3 per condition).
2023-07-01 | GSE210046 | GEO
Project description:Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS) with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused my methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. While toxins have never been clearly indicated in CNS infections, our study shows that an important type of infection caused by the predominant CNS species, S. epidermidis, is mediated to a large extent by a toxin. Of note, these findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches. We used microarrays to detail the global gene expression between S. epidermidis strain Rp62A and S. epidermidis strain Rp62A isogenic Δpsm-mec deletion mutants
2017-01-06 | GSE85265 | GEO
Project description:Autoinducer 2 (AI-2), a widespread by-product of the LuxS-catalyzed S-ribosylhomocysteine cleavage reaction in the activated methyl cycle, has been suggested to serve as an intra- and interspecies signaling molecule, but in many bacteria AI-2 control of gene expression is not completely understood. Particularly, we have a lack of knowledge about AI-2 signaling in the important human pathogens Staphylococcus aureus and S. epidermidis. Here, to determine the role of LuxS and AI-2 in S. epidermidis, we analyzed genome-wide changes in gene expression in an S. epidermidis luxS mutant and after addition of AI-2 synthesized by over-expressed S. epidermidis Pfs and LuxS enzymes. Genes under AI-2 control included mostly genes involved in sugar, nucleotide, amino acid, and nitrogen metabolism, but also virulence-associated genes coding for lipase and bacterial apoptosis proteins. In addition, we demonstrate by liquid chromatography/mass-spectrometry of culture filtrates that the pro-inflammatory phenol-soluble modulin (PSM) peptides, key virulence factors of S. epidermidis, are under luxS/AI-2 control. Our results provide a detailed molecular basis for the role of LuxS in S. epidermidis virulence and suggest a signaling function for AI-2 in this bacterium. Keywords: wild type without glucose control vs luxS mutant vs luxS mutant with auto-inducer II wild type without glucose control vs luxS mutant vs luxS mutant with auto-inducer II
2008-10-10 | E-GEOD-9427 | biostudies-arrayexpress
Project description:Autoinducer 2 (AI-2), a widespread by-product of the LuxS-catalyzed S-ribosylhomocysteine cleavage reaction in the activated methyl cycle, has been suggested to serve as an intra- and interspecies signaling molecule, but in many bacteria AI-2 control of gene expression is not completely understood. Particularly, we have a lack of knowledge about AI-2 signaling in the important human pathogens Staphylococcus aureus and S. epidermidis. Here, to determine the role of LuxS and AI-2 in S. epidermidis, we analyzed genome-wide changes in gene expression in an S. epidermidis luxS mutant and after addition of AI-2 synthesized by over-expressed S. epidermidis Pfs and LuxS enzymes. Genes under AI-2 control included mostly genes involved in sugar, nucleotide, amino acid, and nitrogen metabolism, but also virulence-associated genes coding for lipase and bacterial apoptosis proteins. In addition, we demonstrate by liquid chromatography/mass-spectrometry of culture filtrates that the pro-inflammatory phenol-soluble modulin (PSM) peptides, key virulence factors of S. epidermidis, are under luxS/AI-2 control. Our results provide a detailed molecular basis for the role of LuxS in S. epidermidis virulence and suggest a signaling function for AI-2 in this bacterium. Keywords: wild type without glucose control vs luxS mutant vs luxS mutant with auto-inducer II
2008-10-10 | GSE9427 | GEO
Project description:Background: Lysine succinylation is a newly identified PTM, which exists widely from prokaryotes to eukaryotes and participates in various cellular processes, especially in the metabolic processes. Staphylococcus epidermidis is a commensal bacterium in the skin, which attracts more attention as a pathogen, especially in immunocompromised patients and neonates by attaching to medical devices and forming biofilms. However, the significance of lysine succinylation in proteins of Staphylococcus epidermidis has not been investigated. Materials and methods: Using antibody affinity enrichment followed by LC-MS/MS analysis, we examined the succinylome of Staphylococcus epidermidis (ATCC®12228™). Then, bioinformatics analysis was performed, including Gene Ontology, KEGG enrichment, motif characterization, secondary structure, protein-protein interaction, and BLAST analysis. Results: A total of 1557 succinylated lysine sites in 649 proteins were identified in Staphylococcus epidermidis (ATCC 12228). Among these succinylation proteins, GO annotation showed that proteins related to metabolic processes and binding activity accounted for the most based on the analysis of biological process and molecular function, respectively. KEGG pathway characterization indicated that proteins associated with the glycolysis/ gluconeogenesis, and citrate cycle (TCA cycle) pathway were more likely to be succinylated. Moreover, 13 conserved motifs were identified. The specific motif KsuD was conserved in model prokaryotes and eukaryotes. Succinylated proteins with this motif were highly enriched in the glycolysis/gluconeogenesis pathway. One succinylation site(K144) was identified in S-ribosylhomocysteine lyase, a key enzyme in the quorum sensing system, indicating the regulatory role succinylation may play in bacterial processes. Furthermore, 15 succinyltransferases and 18 desuccinylases(erasers) were predicted in S.epidermidis by BLAST analysis. Conclusions: We performed the first comprehensive profile of succinylation in Staphylococcus epidermidis and illustrated the significant role succinylation may play in energy metabolism, QS system, and other bacterial behaviors. This study may be a fundamental basis to investigate the underlying mechanisms of colonization, virulence, and infection of S. epidermidis, as well as provide a new insight into regulatory effects succinylation may lay on metabolic processes.
2021-02-25 | PXD022866 | Pride