Comparison of the oxacillin stress response in vraS and vraT mutants
Ontology highlight
ABSTRACT:
ORGANISM(S): Staphylococcus aureus subsp. aureus USA300
SUBMITTER: Susan Boyle-Vavra
PROVIDER: E-GEOD-39627 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:S. aureus ATCC 25923 is performance standard for antimicrobial susceptibility testing. S. aureus ATCC 33591 showed resistance against erytrhromycin, penicillin, and streptomycin. We used microarray to compare RNA expression between sensitive and resistant strain of S. aureus as a preliminary research for MRSA inhibition. S. aureus strains were cultivated in tryptic soy broth at 37℃ for 18hrs and harvested for RNA extraction and hybridization on Affymetrix microarrays.
2010-09-15 | E-GEOD-18289 | biostudies-arrayexpress
Project description:Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote bacteremia and survival in human blood is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Culture supernatants derived from a USA300 isogenic hlgABC-deletion strain (LAC?hlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Compared with the wild-type USA300 strain (LAC), LAC?hlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LAC?hlgABC strains caused virtually identical disease in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed significant functional redundancy among two-component leukotoxins in vitro. These findings may explain in part the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence. S. aureus strain USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB): time course.
2011-08-25 | E-GEOD-25454 | biostudies-arrayexpress
Project description:The precise mechanism and effects of antibiotics in host gene expression and immunomodulation in MRSA infection is unknown. Using a well characterized Methicillin Resistant Staphylococcus aureus (MRSA) isolate USA300 in a murine model of infection, we determined that linezolid and vancomycin induced differential production of bacterial toxins and host cytokines, differences in host gene expression, and differences in immunomodulators during MRSA bloodstream infection. A total of 35 A/J mice, categorized into seven groups (no infection; no infection with linezolid; no infection with vancomycin; 2 hour post-infection (hpi) S. aureus; 24 hpi S. aureus; 24 hpi S. aureus with linezolid; and 24 hpi S. aureus with vancomycin), were used in this study. Mice were injected with USA300 (6 x 106 CFU/g via i.p. route), then intravenously treated with linezolid (25 mg/kg) or vancomycin (25 mg/kg) at 2 hpi. Control and S. aureus infected mice were euthanized at each time point (2 h or 24h) following injection. Whole blood RNA was used for microarray; three cytokines and two S. aureus toxins [PantonValentine Leukocidin (PVL) and alpha hemolysin] were quantified in mouse serum by ELISA. S. aureus CFUs were significantly reduced in blood and kidney after linezolid or vancomycin treatment in S. aureus-infected mice. In vivo IL-1M-NM-2 in mouse serum was significantly reduced in both linezolid (p=0.001) and vancomycin (p=0.006) treated mice compared to untreated ones. IL-6 was significantly reduced only in linezolid treated (p<0.001) but not in vancomycin treated mice. However, another proinflammatory cytokine, TNF-M-NM-1, did not exhibit altered levels in either linezolid or vancomycin treated mice (p=0.3 and p=0.51 respectively). In vivo level of bacterial toxin, Panton-Valentine leukocidin, in mouse serum was significantly reduced only in linezolid treated mice (p=0.02) but not in vancomycin treated mice. There was no significant effect of either treatment in in vivo level of alpha hemolysin production. Unsupervised hierarchical clustering using the gene expression data from 35 microarrays revealed distinct clustering based on infection status and treatment group. Study of the antibiotic-specific difference in gene expression identified the number of genes uniquely expressed in response to S. aureus infection, infection with linezolid treatment, and infection with vancomycin treatment. Pathway associations study for the differentially expressed genes in each comparison group (Control vs. 24 h S. aureus infection, 24 h S. aureus infection vs. 24 h S. aureus linezolid, and 24 h S. aureus infection vs. 24 h S. aureus vancomycin) in mice using Kyoto Encyclopedia of Genes and Genomes (KEGG) identified toll-like receptor signaling pathway to be common to every comparison groups studied. Glycerolipid metabolism pathway was uniquely associated only with linezolid treatment comparison group. The findings of this study provide the evidence that protein synthesis inhibitor like linezolid does a better job in treating MRSA sepsis compared to cell wall acting antibiotics like vancomycin. To identify differences in host gene expression in a murine sepsis model treated with a) linezolid and b) vancomycin, we used whole blood gene expression (RNA) signatures from A/J inbred mice infected with USA 300 MRSA to evaluate differences in host gene expression among mice treated with linezolid and vancomycin. We used 5 RNA samples from MRSA-infected, linezolid- or vancomycin-treated mice. A total of 7 experimental groups have been employed: 1) Uninfected control group: (negative controls). 2) Uninfected, linezolid-treated group: Uninfected, linezolid-treated mice. 3) Uninfected vancomycin-treated group: Uninfected, vancomycin-treated mice. 4) Infected control group (positive control 2 h) MRSA-infected, untreated mice. 5) Infected control group (positive control 24 h): MRSA-infected, untreated mice. 6) Infected linezolid group: MRSA-infected, linezolid-treated mice. 7) Infected vancomycin group: MRSA-infected, vancomycin-treated mice.
2014-06-05 | E-GEOD-38531 | 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:In the community and clinical settings MRSA infections are more commonly caused by a USA300 strain vs a USA400 strain. The study aims to compare gene expression patterns of Staphyloccoccus aureus USA300(reference) vs USA400(query) and to determine why USA400 is being replaced by a USA300 strain.
2011-04-08 | GSE26255 | 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:Compilation fo whole genome gene expression changes in Staphylococcus aureus USA300 LAC cultures grown in the presence of vehicle or the anti-gout drug benzbromarone. The drug was intially screened as effective against the agr quorum sensing system in Staphylococcus aureus AH1677. A microarray study using total RNA harvested from three cultures of Staphylococcus aureus USA300 LAC plus vehicle control and three cultures of Staphylococcus aureus USA300 LAC plus 12 uM benzbromarone.
2014-03-19 | E-GEOD-55980 | biostudies-arrayexpress
Project description:The study aims to identify genes associated with oxacilin resistance. Staphylococcus aureus USA300 (also referred as 923) is used as reference strain through the whole study. 10 arrays total.
2011-04-08 | E-GEOD-26258 | biostudies-arrayexpress
Project description:More than 200 direct CodY target genes in Staphylococcus aureus were identified by genome-wide analysis of in vitro DNA binding. This analysis, which was confirmed for some genes by DNase I footprinting assays, revealed that CodY is a direct regulator of numerous transcription units associated with amino acid biosynthesis, transport of macromolecules and virulence. The virulence genes regulated by CodY fell into three groups. One group was dependent on the Agr system for its expression; these genes were indirectly regulated by CodY through its repression of the agr locus. A second group was regulated directly by CodY. The third group, which includes genes for alpha-toxin and capsule synthesis, was regulated by CodY in two ways, i.e., by direct repression and by repression of the agr locus. Since S. aureus CodY was activated in vitro by the branched chain amino acids and GTP, CodY appears to link changes in intracellular metabolite pools with the induction of numerous adaptive responses, including virulence. Affymetrix GeneChips were used to compare the transcript titers of S. aureus strains UAMS-1 (wild type) and corresponding agr- (strain CM18), codY- (strain MS1), and agr- codY- (strain CM19) isogenic mutant strains during exponential and stationary phase growth. At least two biological replicates were assessed for each strain and each growth phase.
2010-04-13 | E-GEOD-20973 | biostudies-arrayexpress
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