Comparative genomics of diagnostic and commensal Staphylococcus pseudintermedius reveals niche adaptation through parallel selection of defense mechanisms

Staphylococcus pseudintermedius is a well-known commensal and pathogen of dogs, with modern clinical diagnostics revealing an expanded host-range that now includes humans. It remains unclear whether differentiation across S. pseudintermedius populations is driven primarily by niche-type or host-species. Here, we sequenced 572 diagnostic and commensal isolates from a hospital, veterinary clinic, and within households in the American Midwest, and performed a comparative genomics investigation contrasting human diagnostic, animal diagnostic, human colonizing, pet colonizing, and surface S. pseudintermedius populations. While S. pseudintermedius is indistinguishable across contexts by core and accessory genome architecture, diagnostic isolates report more encoded and phenotypic resistance, while colonizing and surface isolates have developed CRISPR defense systems reflective of common household exposures. We further show that household isolates that persist through anti-staphylococcal decolonization accrue adaptive mutations in defense genes associated with reduced drug susceptibility. Together we report parallel niche-specific bolstering of defense mechanisms through gene acquisition or mutation.