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The mutational landscape of Staphylococcus aureus during colonisation
Francesc Coll1,2,3, Beth Blane4, Katherine L Bellis5,4
1Applied Microbial Genomics Unit, Department of Molecular Basis of Disease, Institute of Biomedicine of Valencia (IBV-CSIC), Valencia, Spain. fcoll@ibv.csic.es.
Nature Communications
|January 13, 2025
Summary
Staphylococcus aureus adapts during human colonization, with key mutations found in metabolic and antibiotic resistance genes. This study reveals evolutionary insights into bacterial persistence and adaptation within a host.
Area of Science:
- Microbiology
- Evolutionary Biology
- Genomics
Background:
- Staphylococcus aureus is a significant human pathogen and commensal organism.
- Bacterial survival and persistence during host colonization are critical drivers of pathogen evolution.
Purpose of the Study:
- To investigate adaptive evolutionary changes in Staphylococcus aureus during human colonization using a genome-wide approach.
- To identify specific genes and metabolic pathways under positive selection in colonization isolates.
Main Methods:
- Genome-wide mutation enrichment analysis of 3060 S. aureus colonization isolates from 791 individuals.
- In vitro validation of phenotypic effects of identified adaptive mutations.
- Inclusion of an additional 4090 isolate genomes for broader analysis.
Main Results:
- An excess of protein-altering mutations was observed in metabolic genes, quorum-sensing regulators (agrA, agrC), and antibiotic targets (fusA, pbp2, dfrA, ileS).
- Nitrogen metabolism, specifically assimilatory nitrite reductase (nasD) and urease (ureG), showed the strongest evidence of adaptation.
- A nasD mutant demonstrated enhanced growth using urea as the sole nitrogen source.
- Eight additional genes, including sasA/sraP, darA/pstA, and rsbU, showed signals of adaptive variation.
Conclusions:
- Staphylococcus aureus exhibits significant adaptive heterogeneity during host colonization.
- Metabolic adaptation, particularly in nitrogen metabolism, is a key feature of S. aureus colonization.
- The study provides a robust methodological framework for investigating host-associated bacterial evolution.
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