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PROVIDER: PRJNA1224029 | 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:Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes.Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.
2022-02-16 | MODEL2007110001 | BioModels
Project description:Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes. Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.
2022-02-16 | MODEL2007150001 | BioModels
Project description:Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes.Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.
2022-02-16 | MODEL2007150002 | BioModels
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:Whole-genome analysis by 62-strain microarray showed variation in resistance and virulence genes on mobile genetic elements (MGEs) between 40 isolates of methicillin-resistant Staphylococcus aureus (MRSA) strain CC22-SCCmecIV but also showed (i) detection of two previously unrecognized MRSA transmission events and (ii) that 7/8 patients were infected with a variant of their own colonizing isolate. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-128]
2012-10-29 | E-BUGS-128 | biostudies-arrayexpress
Project description:Whole genome sequencing of methicillin-resistant Staphylococcus aureus.
| PRJNA895753 | ENA