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PROVIDER: PRJNA1294587 | ENA |
REPOSITORIES: ENA
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Project description:Becker2005 - Genome-scale metabolic network
of Staphylococcus aureus (iSB619)
This model is described in the article:
Genome-scale reconstruction
of the metabolic network in Staphylococcus aureus N315: an
initial draft to the two-dimensional annotation.
Becker SA, Palsson BØ.
BMC Microbiol. 2005; 5: 8
Abstract:
BACKGROUND: Several strains of bacteria have sequenced and
annotated genomes, which have been used in conjunction with
biochemical and physiological data to reconstruct genome-scale
metabolic networks. Such reconstruction amounts to a
two-dimensional annotation of the genome. These networks have
been analyzed with a constraint-based formalism and a variety
of biologically meaningful results have emerged. Staphylococcus
aureus is a pathogenic bacterium that has evolved resistance to
many antibiotics, representing a significant health care
concern. We present the first manually curated elementally and
charge balanced genome-scale reconstruction and model of S.
aureus' metabolic networks and compute some of its properties.
RESULTS: We reconstructed a genome-scale metabolic network of
S. aureus strain N315. This reconstruction, termed iSB619,
consists of 619 genes that catalyze 640 metabolic reactions.
For 91% of the reactions, open reading frames are explicitly
linked to proteins and to the reaction. All but three of the
metabolic reactions are both charge and elementally balanced.
The reaction list is the most complete to date for this
pathogen. When the capabilities of the reconstructed network
were analyzed in the context of maximal growth, we formed
hypotheses regarding growth requirements, the efficiency of
growth on different carbon sources, and potential drug targets.
These hypotheses can be tested experimentally and the data
gathered can be used to improve subsequent versions of the
reconstruction. CONCLUSION: iSB619 represents comprehensive
biochemically and genetically structured information about the
metabolism of S. aureus to date. The reconstructed metabolic
network can be used to predict cellular phenotypes and thus
advance our understanding of a troublesome pathogen.
This model is hosted on
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MODEL1507180070.
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2024-10-15 | MODEL1507180070 | BioModels
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.
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