Many thanks to all co-authors contributed to this work: Beth Blane, Katie Bellis, Marta Matuszewska, Toska Wonfor, Dorota Jamrozy, Michelle Toleman, Joan Geoghegan, @julianparkhill.bsky.social, Ruth Massey, Sharon Peacock, @ewanharrison.bsky.social

Our study also identified several uncharacterised genes that may be critical for colonisation that warrant further experimental investigation.

We also found mutations in genes that could influence how S. aureus interact with human cells or the immune system, such as in genes encoding SraP/SasA and TarS.

Nitrogen metabolism showed the strongest evidence of adaptation, with genes encoding sub-units of the assimilatory nitrite reductase (nasD/nirB) and urease (ureG), and a nitrogen regulatory protein (darA/pstA), showing the highest mutational enrichment.

We observed an excess of protein-altering mutations in metabolic genes, in the Agr system and in antibiotic targets; and showed the phenotypic effect of multiple adaptive mutations including changes in haemolytic activity, antibiotic susceptibility, and metabolite utilisation.

We applied a genome-wide mutation enrichment approach to identify genes in the S. aureus genome under parallel and convergent evolution that could represent signals of adaptation during colonisation.

We analysed the genomes of more than 7,000 Staphylococcus aureus isolates obtained from over 1,500 human carriers to identify genetic changes that originated in the bacteria in its host and natural environment.