The mutational landscape of Staphylococcus aureus during colonisation
Abstract Staphylococcus aureus is an important human pathogen and a commensal of the human nose and skin. Survival and persistence during colonisation are likely major drivers of S. aureus evolution. Here we applied a genome-wide mutation enrichment approach to a genomic dataset of 3060 S. aureus co...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55186-x |
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| author | Francesc Coll Beth Blane Katherine L. Bellis Marta Matuszewska Toska Wonfor Dorota Jamrozy Michelle S. Toleman Joan A. Geoghegan Julian Parkhill Ruth C. Massey Sharon J. Peacock Ewan M. Harrison |
| author_facet | Francesc Coll Beth Blane Katherine L. Bellis Marta Matuszewska Toska Wonfor Dorota Jamrozy Michelle S. Toleman Joan A. Geoghegan Julian Parkhill Ruth C. Massey Sharon J. Peacock Ewan M. Harrison |
| author_sort | Francesc Coll |
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| description | Abstract Staphylococcus aureus is an important human pathogen and a commensal of the human nose and skin. Survival and persistence during colonisation are likely major drivers of S. aureus evolution. Here we applied a genome-wide mutation enrichment approach to a genomic dataset of 3060 S. aureus colonization isolates from 791 individuals. Despite limited within-host genetic diversity, we observed an excess of protein-altering mutations in metabolic genes, in regulators of quorum-sensing (agrA and agrC) and in known antibiotic targets (fusA, pbp2, dfrA and ileS). We demonstrated the phenotypic effect of multiple adaptive mutations in vitro, including changes in haemolytic activity, antibiotic susceptibility, and metabolite utilisation. Nitrogen metabolism showed the strongest evidence of adaptation, with the assimilatory nitrite reductase (nasD) and urease (ureG) showing the highest mutational enrichment. We identified a nasD natural mutant with enhanced growth under urea as the sole nitrogen source. Inclusion of 4090 additional isolate genomes from 731 individuals revealed eight more genes including sasA/sraP, darA/pstA, and rsbU with signals of adaptive variation that warrant further characterisation. Our study provides a comprehensive picture of the heterogeneity of S. aureus adaptive changes during colonisation, and a robust methodological approach applicable to study in host adaptive evolution in other bacterial pathogens. |
| format | Article |
| id | doaj-art-5b3f615c5b7d484f947d92f9bb1b412c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-5b3f615c5b7d484f947d92f9bb1b412c2025-01-19T12:30:35ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-024-55186-xThe mutational landscape of Staphylococcus aureus during colonisationFrancesc Coll0Beth Blane1Katherine L. Bellis2Marta Matuszewska3Toska Wonfor4Dorota Jamrozy5Michelle S. Toleman6Joan A. Geoghegan7Julian Parkhill8Ruth C. Massey9Sharon J. Peacock10Ewan M. Harrison11Applied Microbial Genomics Unit, Department of Molecular Basis of Disease, Institute of Biomedicine of Valencia (IBV-CSIC)Department of Medicine, University of CambridgeParasites & Microbes Programme, Wellcome Sanger InstituteDepartment of Medicine, University of CambridgeInstitute of Microbiology and Infection, University of BirminghamParasites & Microbes Programme, Wellcome Sanger InstituteDepartment of Medicine, University of CambridgeInstitute of Microbiology and Infection, University of BirminghamDepartment of Veterinary Medicine, University of CambridgeSchool of Cellular and Molecular Medicine, University of BristolDepartment of Medicine, University of CambridgeParasites & Microbes Programme, Wellcome Sanger InstituteAbstract Staphylococcus aureus is an important human pathogen and a commensal of the human nose and skin. Survival and persistence during colonisation are likely major drivers of S. aureus evolution. Here we applied a genome-wide mutation enrichment approach to a genomic dataset of 3060 S. aureus colonization isolates from 791 individuals. Despite limited within-host genetic diversity, we observed an excess of protein-altering mutations in metabolic genes, in regulators of quorum-sensing (agrA and agrC) and in known antibiotic targets (fusA, pbp2, dfrA and ileS). We demonstrated the phenotypic effect of multiple adaptive mutations in vitro, including changes in haemolytic activity, antibiotic susceptibility, and metabolite utilisation. Nitrogen metabolism showed the strongest evidence of adaptation, with the assimilatory nitrite reductase (nasD) and urease (ureG) showing the highest mutational enrichment. We identified a nasD natural mutant with enhanced growth under urea as the sole nitrogen source. Inclusion of 4090 additional isolate genomes from 731 individuals revealed eight more genes including sasA/sraP, darA/pstA, and rsbU with signals of adaptive variation that warrant further characterisation. Our study provides a comprehensive picture of the heterogeneity of S. aureus adaptive changes during colonisation, and a robust methodological approach applicable to study in host adaptive evolution in other bacterial pathogens.https://doi.org/10.1038/s41467-024-55186-x |
| spellingShingle | Francesc Coll Beth Blane Katherine L. Bellis Marta Matuszewska Toska Wonfor Dorota Jamrozy Michelle S. Toleman Joan A. Geoghegan Julian Parkhill Ruth C. Massey Sharon J. Peacock Ewan M. Harrison The mutational landscape of Staphylococcus aureus during colonisation Nature Communications |
| title | The mutational landscape of Staphylococcus aureus during colonisation |
| title_full | The mutational landscape of Staphylococcus aureus during colonisation |
| title_fullStr | The mutational landscape of Staphylococcus aureus during colonisation |
| title_full_unstemmed | The mutational landscape of Staphylococcus aureus during colonisation |
| title_short | The mutational landscape of Staphylococcus aureus during colonisation |
| title_sort | mutational landscape of staphylococcus aureus during colonisation |
| url | https://doi.org/10.1038/s41467-024-55186-x |
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