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Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity
Open accessAbstract
Staphylococcus aureus is a preeminent bacterial pathogen capable of colonizing diverse ecological niches within its human host. We describe here the pangenome of S. aureus based on analysis of genome sequences from 64 strains of S. aureus spanning a range of ecological niches, host types, and antibiotic resistance profiles. Based on this set, S. aureus is expected to have an open pangenome composed of 7,411 genes and a core genome composed of 1,441 genes. Metabolism was highly conserved in this core genome; however, differences were identified in amino acid and nucleotide biosynthesis pathways between the strains. Genome-scale models (GEMs) of metabolism were constructed for the 64 strains of S. aureus These GEMs enabled a systems approach to characterizing the core metabolic and panmetabolic capabilities of the S. aureus species. All models were predicted to be auxotrophic for the vitamins niacin (vitamin B3) and thiamin (vitamin B1), whereas strain-specific auxotrophies were predicted for riboflavin (vitamin B2), guanosine, leucine, methionine, and cysteine, among others. GEMs were used to systematically analyze growth capabilities in more than 300 different growth-supporting environments. The results identified metabolic capabilities linked to pathogenic traits and virulence acquisitions. Such traits can be used to differentiate strains responsible for mild vs. severe infections and preference for hosts (e.g., animals vs. humans). Genome-scale analysis of multiple strains of a species can thus be used to identify metabolic determinants of virulence and increase our understanding of why certain strains of this deadly pathogen have spread rapidly throughout the world.
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“For example, Bosi et al [24], included information from all the aforementioned databases to reconstruct 64 models of Staphylococcus aureus.”
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Metadata
- Authors
- Bosi, E., Monk, J. M., Aziz, R. K., Fondi, M., Nizet, V., & Palsson, B. Ø.
- Affiliations
- University of Florence (IT)
- University of California San Diego (US)
- Cairo University (EG)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-06-10
- Volume
- 113
- Issue
- 26
- Pages
- E3801-9
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4932939
- OpenAlex
- W2419335772
- Cited by
- 266
- References
- 104
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 20 · 2023: 19 · 2022: 28 · 2021: 47 · 2020: 41 · 2019: 42 · 2018: 22 · 2017: 17 · 2016: 2
- FWCI
- 14.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- NIH (1R01GM057089)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Staphylococcus aureus, pan-genome, genome-scale metabolic models, auxotrophy, amino acid biosynthesis, nucleotide synthesis, host preference, ecological niche, antibiotic resistance, core genome, pathogenicity
- MeSH terms
- Models, Molecular, Species Specificity, Staphylococcus aureus, Genome, Bacterial, Virulence Factors
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