An Integrated Computational and Experimental Study to Investigate Staphylococcus Aureus Metabolism

Authors

Mohammad Mazharul Islam, University of Nebraska - Lincoln
Vinai Chittezham Thomas, University of Nebraska Medical CenterFollow
Matthew Van Beek, University of Nebraska - Lincoln
Jong-Sam Ahn, University of Nebraska Medical CenterFollow
Abdulelah A. Alqarzaee, University of Nebraska Medical CenterFollow
Chunyi Zhou, University of Nebraska Medical CenterFollow
Paul D. Fey, University of Nebraska Medical CenterFollow
Kenneth W. Bayles, University of Nebraska Medical CenterFollow
Rajib Saha, University of Nebraska - Lincoln

Document Type

Article

Journal Title

NPJ Systems Biology and Applications

Publication Date

2020

Volume

6

Abstract

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.

DOI Link

10.1038/s41540-019-0122-3

ISSN

2056-7189

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Mazharul Islam, Mohammad; Chittezham Thomas, Vinai; Van Beek, Matthew; Ahn, Jong-Sam; Alqarzaee, Abdulelah A.; Zhou, Chunyi; Fey, Paul D.; Bayles, Kenneth W.; and Saha, Rajib, "An Integrated Computational and Experimental Study to Investigate Staphylococcus Aureus Metabolism" (2020). Journal Articles: Pathology and Microbiology. 69.
https://digitalcommons.unmc.edu/com_pathmicro_articles/69