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The mutational landscape of Staphylococcus aureus during colonisation

Author

Listed:
  • Francesc Coll

    (Institute of Biomedicine of Valencia (IBV-CSIC)
    London School of Hygiene & Tropical Medicine
    Wellcome Sanger Institute)

  • Beth Blane

    (University of Cambridge)

  • Katherine L. Bellis

    (Wellcome Sanger Institute
    University of Cambridge)

  • Marta Matuszewska

    (University of Cambridge
    University of Cambridge)

  • Toska Wonfor

    (University of Birmingham
    University of Birmingham)

  • Dorota Jamrozy

    (Wellcome Sanger Institute)

  • Michelle S. Toleman

    (University of Cambridge)

  • Joan A. Geoghegan

    (University of Birmingham
    University of Birmingham
    Trinity College Dublin)

  • Julian Parkhill

    (University of Cambridge)

  • Ruth C. Massey

    (University of Bristol
    University College Cork
    University College Cork)

  • Sharon J. Peacock

    (University of Cambridge)

  • Ewan M. Harrison

    (Wellcome Sanger Institute
    University of Cambridge
    University of Cambridge)

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.

Suggested Citation

  • 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 & , 2025. "The mutational landscape of Staphylococcus aureus during colonisation," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55186-x
    DOI: 10.1038/s41467-024-55186-x
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    References listed on IDEAS

    as
    1. Gavin K. Paterson & Ewan M. Harrison & Gemma G. R. Murray & John J. Welch & James H. Warland & Matthew T. G. Holden & Fiona J. E. Morgan & Xiaoliang Ba & Gerrit Koop & Simon R. Harris & Duncan J. Mask, 2015. "Capturing the cloud of diversity reveals complexity and heterogeneity of MRSA carriage, infection and transmission," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    2. Thaina M. Costa & Albertus Viljoen & Aisling M. Towell & Yves F. Dufrêne & Joan A. Geoghegan, 2022. "Fibronectin binding protein B binds to loricrin and promotes corneocyte adhesion by Staphylococcus aureus," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Olga Tosas Auguet & Jason R Betley & Richard A Stabler & Amita Patel & Avgousta Ioannou & Helene Marbach & Pasco Hearn & Anna Aryee & Simon D Goldenberg & Jonathan A Otter & Nergish Desai & Tacim Kara, 2016. "Evidence for Community Transmission of Community-Associated but Not Health-Care-Associated Methicillin-Resistant Staphylococcus Aureus Strains Linked to Social and Material Deprivation: Spatial Analys," PLOS Medicine, Public Library of Science, vol. 13(1), pages 1-24, January.
    4. Richard G. Everitt & Xavier Didelot & Elizabeth M. Batty & Ruth R Miller & Kyle Knox & Bernadette C. Young & Rory Bowden & Adam Auton & Antonina Votintseva & Hanna Larner-Svensson & Jane Charlesworth , 2014. "Mobile elements drive recombination hotspots in the core genome of Staphylococcus aureus," Nature Communications, Nature, vol. 5(1), pages 1-9, September.
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