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The increasing antibiotic resistance of NTS bacteria has attracted a lot of research on understanding their modus operandi during infection. Growth in the gut lumen is a critical phase of the NTS infection. This might offer opportunities for intervention. However, the metabolic richness of the gut lumen environment and the inherent complexity and robustness of the metabolism of NTS bacteria call for modeling approaches to guide research efforts. In this study, we reconstructed a thermodynamically constrained and context-specific genome-scale metabolic model (GEM) for <jats:italic>S.<\/jats:italic> Typhimurium SL1344, a model strain well-studied in infection research. We combined sequence annotation, optimization methods and in <jats:italic>vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experimental data. We used GEM to explore the nutritional requirements, the growth limiting metabolic genes, and the metabolic pathway usage of NTS bacteria in a rich environment simulating the murine gut. This work provides insight and hypotheses on the biochemical capabilities and requirements of SL1344 beyond the knowledge acquired through conventional sequence annotation and can inform future research aimed at better understanding NTS metabolism and identifying potential targets for infection prevention.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012869","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T17:27:47Z","timestamp":1741714067000},"page":"e1012869","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolic network reconstruction as a resource for analyzing Salmonella Typhimurium SL1344 growth in the mouse 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limits Salmonella Typhimurium infections after diet shifts and fat-mediated microbiota perturbation in mice","volume":"4","author":"SY Wotzka","year":"2019","journal-title":"Nat Microbiol"},{"key":"pcbi.1012869.ref029","article-title":"Enzyme promiscuous profiles for protein sequence and reaction annotation","author":"H MohammadiPeyhani","year":"2023","journal-title":"bioRxiv"},{"issue":"11","key":"pcbi.1012869.ref030","doi-asserted-by":"crossref","first-page":"e1005338","DOI":"10.1371\/journal.ppat.1005262","article-title":"RNA-seq brings new insights to the intra-macrophage transcriptome of Salmonella Typhimurium","volume":"11","author":"S Srikumar","year":"2015","journal-title":"PLoS Pathogens"},{"issue":"6","key":"pcbi.1012869.ref031","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.chom.2013.11.010","article-title":"An infection-relevant transcriptomic compendium for Salmonella enterica Serovar Typhimurium","volume":"14","author":"C Kr\u00f6ger","year":"2013","journal-title":"Cell Host Microbe"},{"issue":"1","key":"pcbi.1012869.ref032","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-22426-3","article-title":"Non-additive microbial community responses to environmental complexity","volume":"12","author":"A Pacheco","year":"2021","journal-title":"Nature Communications"},{"issue":"20","key":"pcbi.1012869.ref033","doi-asserted-by":"crossref","first-page":"E1277-86","DOI":"10.1073\/pnas.1201061109","article-title":"The transcriptional landscape and small RNAs of Salmonella enterica serovar Typhimurium","volume":"109","author":"C Kr\u00f6ger","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6858","key":"pcbi.1012869.ref034","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/35101614","article-title":"Complete genome sequence of Salmonella enterica serovar Typhimurium LT2","volume":"413","author":"M McClelland","year":"2001","journal-title":"Nature"},{"issue":"1","key":"pcbi.1012869.ref035","doi-asserted-by":"crossref","first-page":"10.1128\/ecosalplus.ESP-0021","DOI":"10.1128\/ecosalplus.esp-0021-2015","article-title":"C4-Dicarboxylate Utilization in Aerobic and Anaerobic Growth","volume":"7","author":"G Unden","year":"2016","journal-title":"EcoSal Plus"},{"issue":"6","key":"pcbi.1012869.ref036","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/ismej.2014.14","article-title":"Phylogenetic distribution of three pathways for propionate production within the human gut microbiota","volume":"8","author":"N Reichardt","year":"2014","journal-title":"ISME J"},{"issue":"3","key":"pcbi.1012869.ref037","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"DJ Morrison","year":"2016","journal-title":"Gut 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pathogenicity","volume":"11","author":"SP Pfister","year":"2020","journal-title":"Nat Commun"},{"issue":"5","key":"pcbi.1012869.ref041","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nchembio.1482","article-title":"Bacterial itaconate degradation promotes pathogenicity","volume":"10","author":"J Sasikaran","year":"2014","journal-title":"Nature Chemical Biology"},{"issue":"1","key":"pcbi.1012869.ref042","first-page":"1","article-title":"Analysis of human metabolism by reducing the complexity of the genome-scale models using redHUMAN","volume":"11","author":"M Masid","year":"2020","journal-title":"Nature Communications"},{"issue":"16","key":"pcbi.1012869.ref043","doi-asserted-by":"crossref","first-page":"5632","DOI":"10.1128\/AEM.00822-15","article-title":"Mesaconase Activity of Class I Fumarase Contributes to Mesaconate Utilization by Burkholderia xenovorans","volume":"81","author":"M Kronen","year":"2015","journal-title":"Appl Environ Microbiol"},{"issue":"2","key":"pcbi.1012869.ref044","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/0005-2795(75)90109-9","article-title":"Comparison of the predicted and observed secondary structure of T4 phage lysozyme","volume":"405","author":"BW Matthews","year":"1975","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"pcbi.1012869.ref045","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1128\/jb.149.3.1171-1174.1982","article-title":"Repression of cytosine deaminase by pyrimidines in Salmonella typhimurium","volume":"149","author":"TP West","year":"1982","journal-title":"J Bacteriol"},{"issue":"2","key":"pcbi.1012869.ref046","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1002\/prot.20997","article-title":"Comparative model of EutB from coenzyme B12-dependent ethanolamine ammonia-lyase reveals a beta8alpha8, TIM-barrel fold and radical catalytic site structural features","volume":"64","author":"S L","year":"2006","journal-title":"Proteins"},{"issue":"5","key":"pcbi.1012869.ref047","doi-asserted-by":"crossref","first-page":"e1004261","DOI":"10.1371\/journal.pcbi.1004261","article-title":"Metabolic needs and capabilities of Toxoplasma gondii through combined computational and experimental analysis","volume":"11","author":"S Tymoshenko","year":"2015","journal-title":"PLoS Computational Biology"},{"issue":"3","key":"pcbi.1012869.ref048","doi-asserted-by":"crossref","first-page":"291-","DOI":"10.1016\/j.chom.2017.07.018","article-title":"An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate","volume":"22","author":"L Spiga","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"4","key":"pcbi.1012869.ref049","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00773-18","article-title":"Host-derived metabolites modulate transcription of salmonella genes involved in L-Lactate utilization during gut colonization","volume":"87","author":"C Gillis","year":"2019","journal-title":"Infection and Immunity"},{"key":"pcbi.1012869.ref050","article-title":"Salmonella Typhimurium screen identifies shifts in mixed-acid fermentation during gut colonization","author":"BD Nguyen","year":"2024","journal-title":"Cell Host Microbe"},{"key":"pcbi.1012869.ref051","article-title":"Monosaccharides drive Salmonella gut colonization in a context-dependent manner","author":"C Schubert","year":"2024","journal-title":"bioRxiv"},{"issue":"39","key":"pcbi.1012869.ref052","doi-asserted-by":"crossref","first-page":"28791","DOI":"10.1074\/jbc.M703759200","article-title":"Genome-scale reconstruction of metabolic network in Bacillus subtilis based on high-throughput phenotyping and gene essentiality data","volume":"282","author":"Y-K Oh","year":"2007","journal-title":"J Biol Chem"},{"issue":"1","key":"pcbi.1012869.ref053","doi-asserted-by":"crossref","first-page":"100280","DOI":"10.1016\/j.xpro.2020.100280","article-title":"PhenoMapping: a protocol to map cellular phenotypes to metabolic bottlenecks, identify conditional essentiality, and curate metabolic models","volume":"2","author":"A Chiappino-Pepe","year":"2021","journal-title":"STAR Protoc"},{"issue":"D1","key":"pcbi.1012869.ref054","first-page":"D320-4","article-title":"TransportDB 2.0: A database for exploring membrane transporters in sequenced genomes from all domains of life","volume":"45","author":"LDH Elbourne","year":"2017","journal-title":"Nucleic Acids Research"},{"issue":"5222","key":"pcbi.1012869.ref055","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1126\/science.7618105","article-title":"Simultaneous identification of bacterial virulence genes by negative selection","volume":"269","author":"M Hensel","year":"1995","journal-title":"Science"},{"key":"pcbi.1012869.ref056","unstructured":"Evangelia V. 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Zenodo. 2024.2024."},{"issue":"1","key":"pcbi.1012869.ref057","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/bioinformatics\/bty499","article-title":"pyTFA and matTFA: a Python package and a Matlab toolbox for thermodynamics-based flux analysis","volume":"35","author":"P Salvy","year":"2018","journal-title":"Bioinformatics"},{"issue":"3","key":"pcbi.1012869.ref058","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1529\/biophysj.107.124784","article-title":"Group contribution method for thermodynamic analysis of complex metabolic networks","volume":"95","author":"M Jankowski","year":"2008","journal-title":"Biophysical Journal"},{"issue":"1","key":"pcbi.1012869.ref059","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/bioinformatics\/bty499","article-title":"pyTFA and matTFA: a Python package and a Matlab toolbox for Thermodynamics-based Flux Analysis","volume":"35","author":"P Salvy","year":"2019","journal-title":"Bioinformatics"},{"key":"pcbi.1012869.ref060","article-title":"Energetics of glucose uptake in Salmonella typhimurium.","author":"M Driessen","year":"1987","journal-title":"Arch Microbiol"},{"issue":"2","key":"pcbi.1012869.ref061","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1057\/jt.2009.5","article-title":"The correlation coefficient: Its values range between 1\/1, or do they","volume":"17","author":"B Ratner","year":"2009","journal-title":"Journal of Targeting, Measurement and Analysis for Marketing"},{"issue":"1","key":"pcbi.1012869.ref062","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12864-019-6413-7","article-title":"The advantages of the Matthews correlation coefficient (MCC) over F1 score and accuracy in binary classification evaluation","volume":"21","author":"D Chicco","year":"2020","journal-title":"BMC Genomics"},{"issue":"46","key":"pcbi.1012869.ref063","doi-asserted-by":"crossref","first-page":"e2211197119","DOI":"10.1073\/pnas.2211197119","article-title":"A workflow for annotating the knowledge gaps in metabolic reconstructions using known and hypothetical reactions","volume":"119","author":"E Vayena","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pcbi.1012869.ref064","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","author":"M Kanehisa","year":"2000","journal-title":"Nucleic Acids Research"},{"key":"pcbi.1012869.ref065","article-title":"ATLASx: a computational map for the exploration of biochemical space","author":"H Mohammadi-Peyhani","year":"2021","journal-title":"bioRxiv"},{"issue":"D1","key":"pcbi.1012869.ref066","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","article-title":"UniProt: the universal protein knowledgebase in 2021","volume":"49","author":"TU Consortium","year":"2021","journal-title":"Nucleic Acids Research"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1012869","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T21:29:52Z","timestamp":1742506192000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012869"}},"subtitle":[],"editor":[{"given":"Mark","family":"Blenner","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":66,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1012869","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1012869","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]}}}