Integrated genomic and functional analyses of human skin–associated Staphylococcus reveal extensive inter- and intra-species diversity

What is it about?

The bacterial genus Staphylococcus is a prominent member of the human skin microbiome, playing an important role in maintenance of healthy skin. The significance and scope of mechanistic studies that aim to identify staphylococcal genes contributing to skin health is often limited without knowledge of the population genetics of skin associated staphylococci. Our work addresses this gap by studying inter- and intra-species staphylococcal diversity present across multiple body sites in a healthy human cohort using a combination of 16S rRNA amplicon sequencing, pan-genomics, and transcriptomic analyses. We found sizeable variation in species representation across individuals, with only four species (S. epidermidis, S. hominis, S. capitis and S. warneri) being present throughout the cohort. Comparative pan-genomics showed that majority of the genes encoded by individual genomes were conserved either between or within species. These genes encoded central metabolic functions as well as those involved in skin colonization. Along with this conserved gene content, we could detect distinct genotypes within each species, each carrying a unique gene set, and displaying specific body site preference. Apart of these shared genes, a large fraction of the pan-genomes encoded strain-specific genes. In addition to pan-genome analysis, RNA-Seq analysis of select staphylococcal isolates grown under skin-like conditions revealed significant differences in gene expression across species and genotypes, further contributing to the observed staphylococcal genetic diversity.

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Why is it important?

Our current study reveals tremendous genetic and functional diversity within the skin associated staphylococci at each taxonomic level across individuals. Characterizing strain-specific genes should help unlock the potential of engineering skin communities with functions that promote health. In addition to this diversity, the study also highlights the presence a sizeable number of genes that are uniquely conserved in each species, potentially allowing species to co-colonize the human skin using distinct molecular pathways. Delineating the function of these conserved genes should shed light on the distinct adaptations in each species that allow successful and stable human skin colonization.

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