Staphylococcus aureus strain:WCH-SK2 SCV
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PROVIDER: PRJNA288081 | ENA |
REPOSITORIES: ENA
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Project description:Respiration deficient S. aureus small colony variants (SCVs) frequently cause persistent infections, which necessitates they acquire iron, yet how SCVs obtain iron remains unknown. To address this, we created a stable hemB mutant in S. aureus USA300 strain LAC. The hemB SCV utilized exogenously supplied heme but was attenuated for growth under conditions of iron starvation. RNA-seq showed that both WT S. aureus and the hemB mutant sense and respond to iron starvation.
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Project description:Heinemann2005 - Genome-scale reconstruction
of Staphylococcus aureus (iMH551)
This model is described in the article:
In silico genome-scale
reconstruction and validation of the Staphylococcus aureus
metabolic network.
Heinemann M, Kümmel A,
Ruinatscha R, Panke S.
Biotechnol. Bioeng. 2005 Dec; 92(7):
850-864
Abstract:
A genome-scale metabolic model of the Gram-positive,
facultative anaerobic opportunistic pathogen Staphylococcus
aureus N315 was constructed based on current genomic data,
literature, and physiological information. The model comprises
774 metabolic processes representing approximately 23% of all
protein-coding regions. The model was extensively validated
against experimental observations and it correctly predicted
main physiological properties of the wild-type strain, such as
aerobic and anaerobic respiration and fermentation. Due to the
frequent involvement of S. aureus in hospital-acquired
bacterial infections combined with its increasing antibiotic
resistance, we also investigated the clinically relevant
phenotype of small colony variants and found that the model
predictions agreed with recent findings of proteome analyses.
This indicates that the model is useful in assisting future
experiments to elucidate the interrelationship of bacterial
metabolism and resistance. To help directing future studies for
novel chemotherapeutic targets, we conducted a large-scale in
silico gene deletion study that identified 158 essential
intracellular reactions. A more detailed analysis showed that
the biosynthesis of glycans and lipids is rather rigid with
respect to circumventing gene deletions, which should make
these areas particularly interesting for antibiotic
development. The combination of this stoichiometric model with
transcriptomic and proteomic data should allow a new quality in
the analysis of clinically relevant organisms and a more
rationalized system-level search for novel drug targets.
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2015-07-30 | MODEL1507180072 | BioModels
Project description:Staphylococcus aureus is one of the most important pathogens in humans and animals, multiply resistant strains are increasingly widespread, new agents are needed for the treatment of S. aureus. Rhein, a natural plant product, has potential antimicrobial activity against Staphylococcus aureus. We employed Affymetrix Staphylococcus aureus GeneChipsTM arrays to investigate the global transcriptional profiling of Staphylococcus aureus ATCC25923 treated with rhein. Results provided insight into mechanisms involved in rhein - Staphylococcus aureus interactions. Keywords: rhein response
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Project description:Staphylococcus aureus (S. aureus) is an important human and animal pathogen, multiply resistant strains are increasingly widespread, new agents are needed for the treatment of S. aureus. magnolol has potent antimicrobial activity against S. aureus. We employed Affymetrix Staphylococcus aureus GeneChipsTM arrays to investigate the global transcriptional profiling of Staphylococcus aureus ATCC25923 treated with magnolol. Keywords: gene expression array-based, count
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Project description:Staphylococcus aureus is a human commensal bacterium and opportunistic pathogen. Chronicity of S. aureus infection has been linked to bacterial survival within host cells including macrophages. Bacteria recovered from the intracellular milieu often form small colony variants (SCV) which are growing slowly, show reduced virulence factor production and are more resistant to antibiotics. Branched chain amino acids (BCAA) are an important class of nutrients for S. aureus. We therefore tested if components of BCAA biosynthesis or transport would alter the outcome of macrophage infection. We found that S. aureus mutants in the BCAA transporter BrnQ1 survived experimental infection of primary human macrophages for the complete duration of the 28 day experiments. Since phenotypic differences between brnQ1 mutants and wild-type bacteria occurred around 10 h p.i., we performed dual RNA-seq by which we determined the transcriptomes of both, pathogen and macrophage host, simultaneously. Our data indicate that at that time transcriptomic changes exclusively are governed by the internalized pathogen. The differential analysis of S. aureus WT and its isogenic brnQ1 mutant surprisingly demonstrated a dysregulation of iron-dependently regulated genes.
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2007-08-10 | GSE8735 | GEO
Project description:Young adult fer-15;fem-1 Caenorhabditis elegans were infected with Staphylococcus aureus for 8 h to determine the transcriptional host response to Staphylococcus aureus. Analysis of differential gene expression in C. elegans young adults exposed to two different bacteria: E. coli strain OP50 (control), wild-type Staphylococcus aureus RN6390. Samples were analyzed at 8 hours after exposure to the different bacteria. These studies identified C. elegans genes induced by pathogen infection. Keywords: response to pathogen infection, innate immunity, host-pathogen interactions
2010-06-12 | GSE21819 | GEO
Project description:Staphylococcus aureus (S. aureus) is an important human and animal pathogen, multiply resistant strains are increasingly widespread, new agents are needed for the treatment of S. aureus. sodium houttuyfonate has potent antimicrobial activity against S. aureus. We employed Affymetrix Staphylococcus aureus GeneChipsTM arrays to investigate the global transcriptional profiling of Staphylococcus aureus ATCC25923 treated with sodium houttuyfonate. Keywords: gene expression array-based, count
2008-10-22 | GSE13233 | GEO
Project description:We have observed that for a number of S. aureus strains as they switch to a SCV lifestyle there is the formation of an extracellular matrix. We focused our analysis on one strain, WCH-SK2. For bacterial survival in the host, the combination of low nutrients and the prolonged timeframe forms a stress that selects for a specific cell-type from the population. In this context, we used steady-state growth conditions with low nutrients and a controlled low growth rate, for a prolonged time and with methylglyoxal. These conditions induced S. aureus WCH-SK2 into a stable SCV cell-type, they did not revert after sub-culturing. Methods: Transcriptomic profiles of wild-type (WT) and SCV were generated in continuous culture in the presence of stress (high and low level of methylglyoxal). Results: Analysis revealed these cells possessed a metabolic and surface profile that was different from previously described SCVs or biofilm cells. The extracellular matrix was protein and extracellular DNA; but not polysaccharide. The SCV cells induced expression of certain surface proteins (such as Ebh) and lantibiotic synthesis while down-regulating factors that stimulates immune response (leucocidin, capsule, carotenoid). We also studied further their genetic characteristics. They possessed an increased viability in the presence of antibiotics compared to their non-SCV form. Their stability implied there had been genetic changes, we determined the whole genome sequence of WCH-SK2 and its stable SCV forms at a single base resolution, employing Single Molecular Real-Time (SMRT) sequencing that also enables the methylome to be determined. The genetic features of this isolate have been identified; the SCCmec type, the pathogenicity and genetic islands and virulence factors. The comparison has identified a set of genetic changes that occurred in the stable SCV form; most notably to the global regulator MgrA and the phosphoserine phosphatase RsbU (part of the regulatory pathway of the sigma factor SigB). There was a shift in the methylation across the genome. Conclusions: Our data reveal a cell heterogeneity within a S. aureus population and using conditions that resemble long-term survival in the host has identified a previously unnoticed S. aureus cell-type, with a distinctive metabolic and molecular profile. The results from this study represent a unique identification of a suite of epigenetic, genetic and transcriptional factors that are implicated in the switch in S. aureus to its persistent SCV form
2014-12-02 | GSE63750 | GEO