The mutational landscape of Staphylococcus aureus during colonisation

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 and Ewan M. Harrison ()
Additional contact information
Francesc Coll: Institute of Biomedicine of Valencia (IBV-CSIC)
Beth Blane: University of Cambridge
Katherine L. Bellis: Wellcome Sanger Institute
Marta Matuszewska: University of Cambridge
Toska Wonfor: University of Birmingham
Dorota Jamrozy: Wellcome Sanger Institute
Michelle S. Toleman: University of Cambridge
Joan A. Geoghegan: University of Birmingham
Julian Parkhill: University of Cambridge
Ruth C. Massey: University of Bristol
Sharon J. Peacock: University of Cambridge
Ewan M. Harrison: Wellcome Sanger Institute

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-55186-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55186-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-55186-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().