Staphylococcus aureus USA300 JE2 evolved to mouse nasopharyngeal colonisation

In this study, a murine nasopharyngeal colonisation model was established and then used for three serial passages of seven days with S. aureus. During the evolutionary timescale, a pronounced genetic variation was identified among the surviving colonising isolates, demonstrating that S. aureus mutations are naturally selected against the selective pressures in the nasopharynx niche. DNA Sequence variants were mainly found in genes that encode proteins with roles in DNA activity and metabolism, with very limited polymorphism found in adhesion and virulence genes. Over the course of this study, intra-species competition for the nasopharynx niche was observed, whereby a S. aureus strain already colonising mice (named SA_MOU) prevented invasion by the experimental S. aureus strain after its inoculation. Although the competitor strains are closely related to USA300 (both belong to ST8), the SA_MOU genome sequence did not reveal strong evidence for similar genetic adaptation to the nasopharynx as that identified via the SNPs of USA300 LAC JE2 after serial passages of the murine nasopharynx. This study has increased our understanding of S. aureus adaptive responses to selective pressures in the nasopharynx, which could contribute to future novel strategies aimed at inhibiting human nasal carriage of S. aureus.