Aureo Wiki ̵ The repository of the Staphylococcus aureus research and annotation community

Fuchs, Stephan; Mehlan, Henry; Bernhardt, Jörg; Hennig, André; Michalik, Stephan; Surmann, Kristin; Pané‐Farré, Jan; Giese, Anne; Weiß, Stefan; Backert, Linus; Herbig, Alexander; Nieselt, Kay; Hecker, Michael; Völker, Uwe; Mäder, Ulrike

doi:10.1016/j.ijmm.2017.11.011

Cited by 95 publications

(96 citation statements)

References 62 publications

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“…EggNOG annotations of all proteins were retrieved from webserver (last accessed 2017-12-15) [59]. Gene names were retrieved from AureoWiki [60] (last accessed 2017-12-15). Extraction of annotations GO, Keywords, EggNOG and Kegg pathway were performed using Perseus.…”

Section: Methodsmentioning

confidence: 99%

Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

Tan

Coureuil

Ramond

et al. 2018

Preprint

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BackgroundChronic lung infection of cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Strikingly the molecular mechanisms underlying S. aureus persistency are not understood.MethodsWe selected pairs of sequential S. aureus isolates from 3 patients with CF and from one patient with non-CF chronic lung disease. We used a combination of genomic, proteomic and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence.ResultsFor the first time, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CFBE-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated.Furthermore, we identified the underlying genetic modifications inducing altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways and virulence regulators that could constitute therapeutic targets.ConclusionsOur results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.SummaryS. aureus persists for years in the lungs of patients with cystic fibrosis despite antibiotic therapies. We demonstrate that S. aureus adaptation leads to increased intracellular persistence suggesting a key role for intracellular niche during S. aureus chronic lung infection.

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Section: Methodsmentioning

confidence: 99%

Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

Tan

Coureuil

Ramond

et al. 2018

Preprint

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“…Checking reactions from the S. aureus N315 model iSB619 20 against the annotations of strain USA300_FPR3757 in the KEGG database 40 resulted in the inclusion of seven unique reactions to the preliminary model. In addition, every reaction in the model was verified for correct gene annotations in the NCBI, KEGG, and UniProt databases and published resources 19,21,[40][41][42][43] to amend the model with 90 metabolic reactions and annotate 75 reactions with correct Gene-Protein-Reaction (GPR) rules.…”

Section: Resultsmentioning

confidence: 99%

An integrated computational and experimental study to investigate Staphylococcus aureus metabolism

et al. 2020

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Staphylococcus aureus is a metabolically versatile pathogen that colonizes nearly all organs of the human body. A detailed and comprehensive knowledge of staphylococcal metabolism is essential to understand its pathogenesis. To this end, we have reconstructed and experimentally validated an updated and enhanced genome-scale metabolic model of S. aureus USA300_FPR3757. The model combined genome annotation data, reaction stoichiometry, and regulation information from biochemical databases and previous strain-specific models. Reactions in the model were checked and fixed to ensure chemical balance and thermodynamic consistency. To further refine the model, growth assessment of 1920 nonessential mutants from the Nebraska Transposon Mutant Library was performed, and metabolite excretion profiles of important mutants in carbon and nitrogen metabolism were determined. The growth and no-growth inconsistencies between the model predictions and in vivo essentiality data were resolved using extensive manual curation based on optimization-based reconciliation algorithms. Upon intensive curation and refinements, the model contains 863 metabolic genes, 1379 metabolites (including 1159 unique metabolites), and 1545 reactions including transport and exchange reactions. To improve the accuracy and predictability of the model to environmental changes, condition-specific regulation information curated from the existing knowledgebase was incorporated. These critical additions improved the model performance significantly in capturing gene essentiality, substrate utilization, and metabolite production capabilities and increased the ability to generate model-based discoveries of therapeutic significance. Use of this highly curated model will enhance the functional utility of omics data, and therefore, serve as a resource to support future investigations of S. aureus and to augment staphylococcal research worldwide.npj Systems Biology and Applications (2020) 6:3 ; https://doi.

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“…Checking reactions from the S. aureus N315 model i SB619 20 against the annotations of strain USA300_FPR3757 in the KEGG database 39 resulted in the inclusion of seven unique reactions to the preliminary model. In addition, every metabolic function in the model was verified for correct gene annotations in the NCBI, KEGG, and UniProt databases and published resources 19,39-42 to amend the model with 38 metabolic reactions and annotate 75 additional reactions with correct Gene-Protein-Reaction (GPR) rules.…”

Section: Resultsmentioning

confidence: 99%

An integrated computational and experimental study to elucidateStaphylococcus aureusmetabolism

Islam

Thomas

Beek

et al. 2019

Preprint

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23Staphylococcus aureus is a metabolically versatile pathogen that colonizes nearly all organs of 24 the human body. A detailed and comprehensive knowledge of staphylococcal metabolism is 25 essential to understanding its pathogenesis. To this end, we have reconstructed and 26 experimentally validated an updated and enhanced genome-scale metabolic model of S. aureus 27 USA300_FPR3757. The model combined genome annotation data, reaction stoichiometry, and 28 regulation information from biochemical databases and previous strain-specific models. 29 Reactions in the model were checked and fixed to ensure chemical balance and thermodynamic 30 consistency. To further refine the model, growth assessment of 1920 non-essential mutants from 31 the Nebraska Transposon Mutant Library was performed and metabolite excretion profiles of 32 important mutants in carbon and nitrogen metabolism were determined. The growth and no-33 growth inconsistencies between the model predictions and in vivo essentiality data were resolved 34 using extensive manual curation based on optimization-based reconciliation algorithms. Upon 35 intensive curation and refinements, the model contains 840 metabolic genes, 1442 metabolites, 36 and 1566 reactions including transport and exchange reactions. To improve the accuracy and 37 predictability of the model to environmental changes, condition-specific regulation information 38 curated from the existing knowledgebase was incorporated. These critical additions improved the 39 model performance significantly in capturing gene essentiality, substrate utilization, and 40 metabolite production capabilities and increased the ability to generate model-based discoveries 41 of therapeutic significance. Use of this highly curated model will enhance the functional utility 42 of omics data and, therefore, serve as a resource to support future investigations of S. aureus and 43 to augment staphylococcal research worldwide. 44 45 3 Keywords: Staphylococcus aureus, genome-scale metabolic model 46 109 Results 110 Reconstruction of an updated model of S. aureus metabolism 111 Preliminary reconstruction utilizing the existing knowledge base 112 A collection of 1511 metabolic reactions obtained from a consensus of recently published strain-113 specific models 19,21 was assembled into a preliminary model of S. aureus. Out of 842 genes in 114 6 the latest strain-specific USA300_FPR3757_uid58555 model by Bosi et al. 19 , 109 did not have 115 any reactions associated with them, which were not included in our model at this stage. Checking 116 reactions from the S. aureus N315 model iSB619 20 against the annotations of strain 117 USA300_FPR3757 in the KEGG database 39 resulted in the inclusion of seven unique reactions to 118 the preliminary model. In addition, every metabolic function in the model was verified for 119 correct gene annotations in the NCBI, KEGG, and UniProt databases and published 120 resources 19,39-42 to amend the model with 38 metabolic reactions and annotate 75 additional 121 reactions with correct Gene-Pr...

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Aureo Wiki ̵ The repository of the Staphylococcus aureus research and annotation community

Cited by 95 publications

References 62 publications

Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

An integrated computational and experimental study to investigate Staphylococcus aureus metabolism

An integrated computational and experimental study to elucidateStaphylococcus aureusmetabolism

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