Genomic and functional divergence of Staphylococcus aureus strains from atopic dermatitis patients and healthy individuals: insights from global and local scales

Atopic dermatitis (AD) is the most common chronic inflammatoryskin disease worldwide and is characterized by a complex interplay with skin microbiota, with Staphylococcus aureus often abnormally more abundant in AD patients than in healthy individuals (HE). S. aureus harbors diverse strains with varied genetic compositions and functionalities, which exhibit differentialconnections with the severity of AD. However, the differencesin S. aureus strains between AD and HE remain unclear, with most variations seen at a specificgeographic level, implying spontaneous adaptations rather than systematic distinctions. This study presents genomic and functional differencesbetween these S. aureus strains from AD and HE on both global and local levels. We observed reduced gene content diversity but increased functional variation in the global AD-associated strains. Two additional AD-dominant clusters emerged, with Cluster 1 enriched in transposases and Cluster 2 showcasing genes linked to adaptability and antibiotic resistance. Particularly, robust evidence illustrates that the lantibiotic operon of S. aureus, involved in the biosynthesis of lantibiotics, was acquired via horizontal gene transfer from environmental bacteria. Comparisons of the gene abundance profilesin functional categories also indicate limited zoonotic potential between human and animal isolates. Local analysis mirrored global gene diversity but showed distinct functional variations between AD and HE strains. Overall, this research provides foundational insights into the genomic evolution, adaptability, and antibiotic resistance of S. aureus, with significantimplications for clinical microbiology.