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

Abstract

Human skin is stably colonized by a distinct microbiota that functions together with epidermal cells to maintain a protective physical barrier. Staphylococcus , a prominent genus of the skin microbiota, participates in colonization resistance, tissue repair, and host immune regulation in strain-specific manners. To unlock the potential of engineering skin microbial communities, we aim to characterize the diversity of this genus within the context of the skin environment. We reanalyzed an extant 16S rRNA amplicon dataset obtained from distinct body sites of healthy volunteers, providing a detailed biogeographic depiction of staphylococcal species that colonize our skin. S. epidermidis , S. capitis, and S. hominis were the most abundant staphylococcal species present in all volunteers and were detected at all body sites. Pan-genome analysis of isolates from these three species revealed that the genus-core was dominated by central metabolism genes. Species-restricted-core genes encoded known host colonization functions. The majority (~68%) of genes were detected only in a fraction of isolate genomes, underscoring the immense strain-specific gene diversity. Conspecific genomes grouped into phylogenetic clades, exhibiting body site preference. Each clade was enriched for distinct gene sets that are potentially involved in site tropism. Finally, we conducted gene expression studies of select isolates showing variable growth phenotypes in skin-like medium. In vitro expression revealed extensive intra- and inter-species gene expression variation, substantially expanding the functional diversification within each species. Our study provides an important resource for future ecological and translational studies to examine the role of shared and strain-specific staphylococcal genes within the skin environment.

Intraspecies warfare restricts strain coexistence in human skin microbiomes

“…Antimicrobial exporters and cell envelope components could be targeted by phage 42 and the immune system 18,45 , imposing harsh selective pressures against antagonists and resistors on certain hosts. Priority effects 12,13 , selection on orthogonal phenotypes 4,46 , and fitness deficits induced by the cost of production may also play important roles, though we find no consistent growth deficit for production or resistance here.…”

“…Despite this potential for transmission, the microbiomes of cohabitating adults do not homogenize 10 , with each individual harboring person-specific strains 11 . Neutral priority effects 12,13 , such as competition with established strains for metabolic 4,14 or spatial niches 15,16 , have been explored as potential drivers of person-specificity. Alternatively, selection for specific species or strains could be driven by the immune system 17,18 , host behavior (e.g.…”

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Determining why only a fraction of encountered or applied bacterial strains engraft in a given person's microbiome is crucial for understanding and engineering these communities 1 . Previous work has established that metabolism can determine colonization success in vivo [2][3][4] , but relevance of bacterial warfare in preventing engraftment has been less explored. Here, we demonstrate that intraspecies warfare presents a significant barrier to strain transmission in the skin microbiome by profiling 14,884 pairwise interactions between Staphylococcus epidermidis cultured from eighteen human subjects from six families.

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Adaptation to skin mycobiota promotes antibiotic tolerance inStaphylococcus aureus

“…S. aureus is a transient colonizer of most epidermal sites, and typically stable colonization occurs typically only in the anterior nares 3, 4 . In contrast, several coagulase negative staphylococci are ubiquitous members of the healthy skin microbiota including Staphylococcus epidermidis, Staphylococcus capitis, and Staphylococcus hominis 47 . As Malassezia are the dominant fungal colonizers of most skin sites, these yeasts likely coexist with commensal staphylococci 19 .…”

Biogeography of the genus Staphylococci on human skin

“…These organisms interact with microbial and host cells in a strain-specific manner to influence the host immune response and tissue repair and promote colonization resistance against pathogenic microbes. In this issue of PNAS, Joglekar et al define the most common members of the Staphylococcal skin microbiome and provide valuable information regarding the physiological role of the Staphylococci in skin health in their manuscript titled “ Integrated genomic and functional analyses of human skin associated Staphylococcus reveals extensive inter- and intra-species diversity ” ( 2 ).…”