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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
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
collection DOAJ
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.
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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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