Staphylococcus aureus
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ABSTRACT:
PROVIDER: PRJNA222833 | ENA |
REPOSITORIES: ENA
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Project description:Several methicillin resistance (SCCmec) clusters characteristic of hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) strains harbor the psm-mec locus. In addition to encoding the cytolysin, phenol-soluble modulin (PSM) mec, this locus has been attributed gene regulatory functions. Here we employed genome-wide transcriptional profiling to define the regulatory function of the psm-mec locus. The immune evasion factor protein A emerged as the primary conserved and strongly regulated target of psm-mec, an effect we show is mediated by the psm-mec RNA. Furthermore, the psm-mec locus exerted regulatory effects that were more moderate in extent and possibly mediated by the PSM-mec peptide. For example, expression of PSM-mec limited expression of mecA, thereby decreasing methicillin resistance. Our study shows that the psm-mec locus has a rare dual regulatory RNA and encoded cytolysin function, both with the potential to enhance MRSA virulence. Furthermore, our findings reveal a specific mechanism underscoring the recently emerging concept that S. aureus strains balance pronounced virulence and high expression of antibiotic resistance.
2017-08-29 | GSE51366 | 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:The Staphylococcus aureus accessory gene regulator (agr) is a prototype quorum-sensing system in Gram-positive bacteria and a paradigmatic example of gene regulation by a small regulatory RNA, RNAIII. Using genome-wide transcriptional profiling in the community-associated methicillin-resistant (CA-MRSA) strain MW2, we demonstrate here that in contrast to the current model of target gene regulation by agr, a large subset of agr-regulated genes is controlled independently of RNAIII. This group comprised predominantly metabolism genes, whereas virulence factors were mostly controlled by RNAIII. Remarkably, the phenol-soluble modulin (PSM) leukocidin genes were the only virulence determinants under RNAIII-independent control, emphasizing their exceptional role in S. aureus physiology and pathogenesis. Of note, PSM promoters bound the AgrA response regulator protein, previously believed to interact exclusively with agr promoters, explaining the exceptionally strict control of PSMs by agr. Our results suggest that virulence factor control is a secondary acquisition of the agr regulon, which evolved by development of RNAIII around the mRNA of the PSM d-toxin, exemplifying how gene control via a small regulatory RNA may be linked to a pre-established regulatory circuit. In addition to elucidating agr control in CA-MRSA, which revealed features potentially crucial for CA-MRSA pathogenesis, our study establishes a novel two-level model of cell-density dependent gene regulation in S. aureus and gives important insight into the connection of metabolism and virulence control in this leading opportunistic pathogen. Keywords: Wild type control vs mutant Wild type in triplicate is compared to mutant in triplicate totalling 27 samples
2010-05-14 | E-GEOD-10165 | biostudies-arrayexpress
Project description:The Staphylococcus aureus accessory gene regulator (agr) is a prototype quorum-sensing system in Gram-positive bacteria and a paradigmatic example of gene regulation by a small regulatory RNA, RNAIII. Using genome-wide transcriptional profiling in the community-associated methicillin-resistant (CA-MRSA) strain MW2, we demonstrate here that in contrast to the current model of target gene regulation by agr, a large subset of agr-regulated genes is controlled independently of RNAIII. This group comprised predominantly metabolism genes, whereas virulence factors were mostly controlled by RNAIII. Remarkably, the phenol-soluble modulin (PSM) leukocidin genes were the only virulence determinants under RNAIII-independent control, emphasizing their exceptional role in S. aureus physiology and pathogenesis. Of note, PSM promoters bound the AgrA response regulator protein, previously believed to interact exclusively with agr promoters, explaining the exceptionally strict control of PSMs by agr. Our results suggest that virulence factor control is a secondary acquisition of the agr regulon, which evolved by development of RNAIII around the mRNA of the PSM d-toxin, exemplifying how gene control via a small regulatory RNA may be linked to a pre-established regulatory circuit. In addition to elucidating agr control in CA-MRSA, which revealed features potentially crucial for CA-MRSA pathogenesis, our study establishes a novel two-level model of cell-density dependent gene regulation in S. aureus and gives important insight into the connection of metabolism and virulence control in this leading opportunistic pathogen. Keywords: Wild type control vs mutant
2009-01-05 | GSE10165 | GEO
Project description:Background: Staphylococcus aureus is a major pathogen of humans and animals. Host genetics influence the susceptibility to S. aureus infections, and genes determining infection outcome remain to be identified. Here, we used outbred animals from a divergent selection on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings: We investigated in vitro how mammary epithelial cells (MEC) respond to live S. aureus or S. aureus supernatant and whether MEC from animals with different degree of susceptibility to intra-mammary infections have distinct gene expression profiles. We measured the expression of 15K probes in MEC after each kind of stimulation (living bacteria or culture supernatant) at three different time points (a reference without bacteria, 1 and 5 hours) with ovine Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. Gene signatures of stimulated MEC were obtained and genes involved in the cell cycle and metabolic processes were down-regulated during the kinetics and the apoptosis pathways were highly modified after both live bacteria and supernatant stimulations. Genes involved in immune response were up-regulated over-all after supernatant exposure. Furthermore 23 genes were differentially expressed between the resistant and susceptible animals, two of them were involed in oxidative processes, but the differences between the animals were very few. Conclusion/Significance: we successfully obtained Staphylococcus aureus associated gene expression of ovine MEC in a 5 hour kinetics experiment. The in vitro MEC model does not provide much information on the differences between Staphylococcus resistant and susceptible animals. Keywords: Staphylococcus aureus ; mammary epithelial cells ; mammalian ; transcriptome ; immunity ; mastitis 59 samples in a two-colour dye-swap experimental design.
2012-03-01 | E-GEOD-30390 | biostudies-arrayexpress
Project description:Background: Staphylococcus aureus is a major pathogen of humans and animals. Host genetics influence the susceptibility to S. aureus infections, and genes determining infection outcome remain to be identified. Here, we used outbred animals from a divergent selection on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings: We investigated in vitro how mammary epithelial cells (MEC) respond to live S. aureus or S. aureus supernatant and whether MEC from animals with different degree of susceptibility to intra-mammary infections have distinct gene expression profiles. We measured the expression of 15K probes in MEC after each kind of stimulation (living bacteria or culture supernatant) at three different time points (a reference without bacteria, 1 and 5 hours) with ovine Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. Gene signatures of stimulated MEC were obtained and genes involved in the cell cycle and metabolic processes were down-regulated during the kinetics and the apoptosis pathways were highly modified after both live bacteria and supernatant stimulations. Genes involved in immune response were up-regulated over-all after supernatant exposure. Furthermore 23 genes were differentially expressed between the resistant and susceptible animals, two of them were involed in oxidative processes, but the differences between the animals were very few. Conclusion/Significance: we successfully obtained Staphylococcus aureus associated gene expression of ovine MEC in a 5 hour kinetics experiment. The in vitro MEC model does not provide much information on the differences between Staphylococcus resistant and susceptible animals. Keywords: Staphylococcus aureus ; mammary epithelial cells ; mammalian ; transcriptome ; immunity ; mastitis
2012-03-01 | GSE30390 | GEO
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) infections result in more than 200,000 hospitalizations and 10,000 deaths in the United States each year and remain an important medical challenge. To better understand the transcriptome of Staphylococcus aureus USA300 NRS384, a community-acquired MRSA strain, we have conducted an RNA-Seq experiment on WT samples.
2017-11-15 | GSE102279 | GEO
Project description:Methicillin-resistant Staphylococcus aureus is one of the major causative agents associated to infections with a high morbidity and mortality in hospitals worldwide. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin isolated and characterized from Larrea tridentata showed the best activity towards methicillin-resistant S. aureus. Understanding of mechanism of action of drugs allows design drugs in a better way. Therefore, we employed microarray to obtain gene expression profile of methicillin-resistant S. aureus after exposure to 3'-demethoxy-6-O-demethylisoguaiacin. The results showed that lignan had an effect on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death.
2015-06-27 | GSE70309 | GEO
Project description:The Impact of CodY on Virulence Determinant Production in Community-Associated Methicillin Resistant Staphylococcus aureus
2012-05-17 | PRD000448 | Pride
Project description:Resolving chromatin remodeling-linked gene expression changes is important for understanding disease states. We describe MAGICAL (Multiome Accessible Gene Integration Calling And Looping), a hierarchical Bayesian approach that leverages paired scRNA-seq and scATAC-seq data from different conditions to map disease-associated transcription factors, regulatory sites and genes as regulatory circuits. By introducing hidden Bayesian variables to allow modeling noise and signal variation across cells and conditions in both transcriptome and chromatin data, in systemic evaluations MAGICAL achieved high accuracy on circuit prediction at cell-type resolution. We applied MAGICAL to study Staphylococcus aureus sepsis from peripheral blood mononuclear single cell data that we generated from infected subjects and healthy uninfected controls. MAGICAL identified sepsis-associated regulatory circuits predominantly in CD14 monocytes, known to be sepsis activated. We addressed the challenging problem of distinguishing methicillin-resistant- (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) infections, where differential expression analysis failed to show predictive value. MAGICAL, however, identified epigenetic circuit biomarkers that distinguished MRSA from MSSA.
2023-05-19 | GSE220189 | GEO