Staphylococcus epidermidis biofilms transcriptome alterations upon incubation with whole human blood
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ABSTRACT:
ORGANISM(S): Staphylococcus epidermidis
PROVIDER: GSE52111 | GEO | 2014/08/29
SECONDARY ACCESSION(S): PRJNA226702
REPOSITORIES: GEO
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Project description:The ability of S. epidermidis to withstand the high bactericidal activity of the hostM-bM-^@M-^Ys blood is crucial for its systemic dissemination. Hence, in order to identify genes and pathways involved in the bacteriumM-bM-^@M-^Ys survival in human blood, we have characterized the transcriptome of S. epidermidis biofilms upon contact with human blood. Our results showed that genes whose transcription was increased in blood included those involved in biosynthesis and metabolism of amino acids, small molecules, carboxylic and organic acids, and cellular ketones. One of the striking changes, observed after 4 hours of exposure to human blood, was the increase in the expression of genes involved in iron utilization, suggesting iron acquisition is an important component of S. epidermidis survival in human blood. Twenty-four hour S. epidermidis biofilms were incubated with either whole human blood or tryptic soy broth (TSB) during 2 or 4 hours at 37oC, 5% CO2 and slight agitation. RNA was then extracted and the transcriptomic libraries constructed. Differential gene expression calculations were performed using the transcriptome of biofilms at the start of the culture (T0h) as a control. This experiment was performed twice with blood collected from 6 healthy human donors under a protocol approved by the PartnerM-bM-^@M-^Ys Health Care System Institutional Review Board (Boston, MA, USA).
2014-08-29 | E-GEOD-52111 | biostudies-arrayexpress
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 among infected patients. In order to better understand the role of BRC in the pathogenesis of S. epidermidis biofilm-related infections, the transcriptome of these cells was evaluated upon exposure to human blood components. The major alterations observed were involved in the biosynthesis and metabolism of amino acids and import and export of substances through ABC transporters. In addition, the transcription of genes involved in biotin metabolism was found significantly up-regulated suggesting this pathway as a possible target for future therapeutic strategies.
2017-02-10 | GSE79948 | GEO
Project description:Proteomic analysis of a commensal Staphylococcus epidermidis strain in different pH conditions for describing the molecular players involved in the skin-to-blood adaptation of the bacterium.
2023-03-11 | PXD034825 | Pride
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: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:To investigate the glycolysis inhibition effect on the inflammation responses of preterm newborns infected with Staphylococcus epidermidis, we used preterm pigs` cord blood to mimic the inflammation condition of preterm newborns at birth and stimulated with S. epidermidis and glycolysis inhibior. We then performed gene expression profiling analysis using data obtained from RNA-seq of the cord blood, which were stimulated with S. epidermidis and DCA.
2022-06-29 | GSE201539 | 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:Newborns, particularly those born prematurely, are extremely vulnerable to sepsis and this has been attributed to ‘immature’ innate monocyte defences. Predominant pathogens include Escherichia. coli and Staphylococcus. epidermidis but no studies have assessed global transcriptional responses of neonatal monocytes to live sepsis-causing bacteria. Here, we aimed to identify and characterise the common and pathogen-specific, neonatal monocyte transcriptional responses to E. coli and S. epidermidis to better understand early life innate immune responses. RNA-sequencing was performed on purified cord blood monocytes from very preterm (<32 weeks gestational age, GA) and term infants (37-40 weeks GA) following standardised challenge with live S. epidermidis or E. coli.
2018-03-16 | GSE101880 | 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