High-resolution Staphylococcus profiling reveals intra-species diversity in a single skin niche

The skin microbiome is dominated by a few key genera, among which Staphylococcus is one of the most well characterized. Recent studies have examined the roles of various Staphylococcus species such as Staphylococcus epidermidis and Staphylococcus hominis within broader skin microbial communities. However, these investigations often rely on isolates from multiple individuals and hence limit their ability to capture intra-community interactions. In this study, we focused on the axillary microbiome of a single healthy individual to characterize the genetic and functional diversity of resident Staphylococcus isolates. Using a low-cost, high-throughput DNA extraction and long-read whole-genome sequencing pipeline, we generated complete genomes for 93 isolates spanning 7 genetically distinct lineages across 3 major skin species. These comprised one dominant and three additional lineages of S. epidermidis , two of S. hominis and one of Staphylococcus capitis . Functional and metabolic analyses revealed species- and strain-specific features, suggesting potential metabolic cross-feeding and specialization within this community, including within strains of S. epidermidis . These findings highlight the metabolic complexity and potential interdependence of staphylococci inhabiting a single skin site and the need for strain-level resolution of the community. The strains form part of the York Skin Microbiome (YSM) collection, a growing open biobank of genetically diverse skin isolates from matched individuals.