|Title||A computational knowledge-base elucidates the response of Staphylococcus aureus to different media types.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Seif Y, Monk JM, Mih N, Tsunemoto H, Poudel S, Zuniga C, Broddrick J, Zengler K, Palsson BO|
|Journal||PLoS Comput Biol|
|PubMed Date||2019 Jan|
S. aureus is classified as a serious threat pathogen and is a priority that guides the discovery and development of new antibiotics. Despite growing knowledge of S. aureus metabolic capabilities, our understanding of its systems-level responses to different media types remains incomplete. Here, we develop a manually reconstructed genome-scale model (GEM-PRO) of metabolism with 3D protein structures for S. aureus USA300 str. JE2 containing 854 genes, 1,440 reactions, 1,327 metabolites and 673 3-dimensional protein structures. Computations were in 85% agreement with gene essentiality data from random barcode transposon site sequencing (RB-TnSeq) and 68% agreement with experimental physiological data. Comparisons of computational predictions with experimental observations highlight: 1) cases of non-essential biomass precursors; 2) metabolic genes subject to transcriptional regulation involved in Staphyloxanthin biosynthesis; 3) the essentiality of purine and amino acid biosynthesis in synthetic physiological media; and 4) a switch to aerobic fermentation upon exposure to extracellular glucose elucidated as a result of integrating time-course of quantitative exo-metabolomics data. An up-to-date GEM-PRO thus serves as a knowledge-based platform to elucidate S. aureus' metabolic response to its environment.
|Alternate Journal||PLoS Comput. Biol.|
A computational knowledge-base elucidates the response of Staphylococcus aureus to different media types.