Staphylococcus aureus
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PROVIDER: PRJNA744410 | ENA |
REPOSITORIES: ENA
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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 (MRSA) is a major threat to human health. Rather than depend on creating new antibiotics (to which bacteria will eventually become resistant), we are employing antibiotic adjuvants that potentiation existing antibiotics. To gain biological insight into how lead compounds potentiate antibiotics and inhibit biofilms, we used RNA-seq on treated MRSA USA300 cultures to examine antibiotic adjuvant affects transcritome-wide.
2025-06-05 | GSE291913 | 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. A key factor of S. aureus pathogenesis is the production of virulence proteins that are secreted into the extracellular matrix damaging host tissues and forming abscesses that may serve as replicative niches for the bacteria. We recently discovered that host-derived cis-unsaturated fatty acids activate the transcription and translation of EsxA, a protein that plays a central role in abscess formation in clinically relevant MRSA strains. Additionally, we discovered that fatty acid stimulation of EsxA is dependent on fakA, a gene that encodes a protein responsible for the incorporation of exogenous fatty acids into the S. aureus phospholipid membrane. In order to gain a comprehensive understanding of host-fatty-acid-sensing in S. aureus, we performed RNA-Seq analysis on WT Staphylococcus aureus USA300 NRS384, a community-acquired MRSA strain, in the presence and absence of 10μM linoleic acid.
2017-11-15 | GSE101580 | GEO
Project description:Little is known about the expression of methicillin-resistant Staphylococcus aureus (MRSA) genes during infection conditions. Here, we described the transcriptome of the clinical MRSA strain USA300 derived from human cutaneous abscesses, and compared it with USA300 bacteria derived from infected kidneys in a mouse model. Remarkable similarity between the transcriptomes allowed us to identify genes encoding multiple proteases and toxins, and iron- and peptide-transporter molecules, which are upregulated in both infections and are likely important for establishment of infection. We also showed that disruption of the global transcriptional regulators agr and sae prevents in vivo upregulation of many toxins and proteases, protecting mice from lethal infection dose, and hinting at the role of these transcriptional regulators in the pathology of MRSA infection.
2015-10-16 | GSE73821 | GEO
Project description:The epidemic community-acquired methicillin-resistant S. aureus (CA-MRSA) clone USA300 has recently become a leading cause of hospital-associated bloodstream infections (BSI). Leveraging this recent introduction into hospitals and the limited genetic variation across the USA300 strains, we combined microbial comparative genomics with phenotypic analyses to discover adaptive mutations. USA300 isolates from BSI were found to have independently evolved single nucleotide variants in the transcriptional regulator sarZ. sarZ inactivation lead to altered expression of virulence factors, resulting in increased lethality in a murine model of BSI. Thus, USA300 strains can optimize their fitness in hospitals through evolution of higher virulence.
2022-10-08 | GSE185544 | GEO
Project description:Introduction Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly isolated, with USA300-0114 being the predominant clone in the USA. Comparative whole genome sequencing of USA300 isolates collected in 2002, 2003 and 2005 showed a limited number of single nucleotide polymorphisms and regions of difference. This suggests that USA300 has undergone rapid clonal expansion without great genomic diversification. However, whole genome comparison of CA-MRSA has been limited to isolates belonging to USA300. The aim of this study was to compare the genetic repertoire of different CA-MRSA clones with that of HA-MRSA from the USA and Europe through comparative genomic hybridization (CGH) to identify genetic clues that may explain the successful and rapid emergence of CA-MRSA. Materials and Methods Hierarchical clustering based on CGH of 48 MRSA isolates from the community and nosocomial infections from Europe and the USA revealed dispersed clustering of the 19 CA-MRSA isolates. This means that these 19 CA-MRSA isolates do not share a unique genetic make-up. Only the PVL genes were commonly present in all CA-MRSA isolates. However, 10 genes were variably present among 14 USA300 isolates. Most of these genes were present on mobile elements. Conclusion The genetic variation present among the 14 USA300 isolates is remarkable considering the fact that the isolates were recovered within one month and originated from a confined geographic area, suggesting continuous evolution of this clone. Data is also available from <ahref=http://bugs.sgul.ac.uk/E-BUGS-108 target=_blank>BuG@Sbase</a>
2011-04-15 | E-BUGS-108 | biostudies-arrayexpress
Project description:Staphylococcus aureus is a Gram-positive human pathogen causing a variety of human diseases in both hospital and community settings. This bacterium is so closely associated with prophages that it is rare to find S. aureus isolates without prophages. Two phages are known to be important for staphylococcal virulence: the beta-hemolysin (hlb) converting phage and the Panton-Valentine Leukocidin (PVL) converting phage. The hlb-converting phage is found in more than 90% of clinical isolates of S. aureus. This phage produces exotoxins and immune modulatory molecules, which inhibit human innate immune responses. The PVL-converting phage produces the two-component exotoxin PVL, which can kill human leucocytes. This phage is wide-spread among community-associated methicillin resistant S. aureus (CA-MRSA). It also shows strong association with soft tissue infections and necrotizing pneumonia. Several lines of evidence suggest that staphylococcal prophages increase bacterial virulence not only by providing virulence factors but also by altering bacterial gene expression: 1) Transposon insertion into prophage regulatory genes, but not into the genes of virulence factors, reduced S. aureus killing of Caenorhabditis elegans.; 2) Although the toxins and immune modulatory molecules encoded by the hlb- converting phages do not function in the murine system, deletion of ϕNM3, the hlb-converting phage in S. aureus Newman, reduced staphylococcal virulence in the murine abscess formation model. 3) In a preliminary microarray experiment, prophages in S. aureus Newman altered the expression of more than 300 genes. In this research proposal, using microarray and high-throughput quantitative RT-PCR (qRT-PCR) technologies, we will identify the effects of the two important staphylococcal phages on the gene expression of S. aureus in both in vitro and in vivo conditions. This project is intended to be completed within one year. All the data – microarray, qRT-PCR and all the primer sequences- will be made available to public 6 month after completion. Data from this project will help us to understand the role of prophages in the S. aureus pathogenesis and can lead to development of a strategy to interfere with the pathogenesis process. Following strains were grown in TSA broth: Staphylococcus aureus USA300 (reference) Staphylococcus aureus USA300 with deletion of ϕSa2usa (Query) Staphylococcus aureus USA300 with deletion of ϕSa3usa (Query) Staphylococcus aureus USA300 Prophage-free mutant (Query) Staphylococcus aureus USA300 Prophage-free mutant lysogenized with ϕSa2mw (Query) Staphylococcus aureus USA300 Prophage-free mutant lysogenized with ϕSa3usa (Query) strain: Staphylococcus aureus USA300 Prophage-free mutant lysogenized with both ϕSa2mw and ϕSa3usa (Query) RNA samples were harvested at early log, midlog and stationary phase.Samples were hybridized on aminosilane coated slides with 70-mer oligos.
2011-02-28 | E-GEOD-26623 | biostudies-arrayexpress
Project description:The success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) as pathogens is due to a combination of antibiotic resistance with high virulence. However, evolution of the exceptional virulence potential of CA-MRSA is not understood. Our previous study indicated that differential gene expression contributes substantially to this process. Thus, we here investigated the role of the pivotal virulence gene regulatory system agr in the most prevalent CA-MRSA strain USA300. Using a mouse subcutaneous infection model, we show that agr is essential for the development of CA-MRSA skin infections, the most frequent manifestation of disease caused by CA-MRSA. Furthermore, genome-wide analysis of gene expression revealed significant differences in agr-dependent virulence gene regulation between CA-MRSA, HA-MRSA, and laboratory strains. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon to optimize expression of a broad set of virulence determinants may have contributed to the evolution of exceptionally pronounced virulence of CA-MRSA strains. Keywords: wild type vs mutant Wild type vs mutant agr strains.
2011-03-29 | E-GEOD-18793 | biostudies-arrayexpress
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 | GSE222548 | GEO
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