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

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide and is characterized by a complex interplay with skin microbiota, with <i>Staphylococcus aureus</i> often abnormally more abundant in AD patients than in healthy individuals (HE). <i>S. aureus</i> harbors diverse strains with varied genetic compositions and functionalities, which exhibit differential connections with the severity of AD. However, the differences in <i>S. aureus</i> strains between AD and HE remain unclear, with most variations seen at a specific geographic level, implying spontaneous adaptations rather than systematic distinctions. This study presents genomic and functional differences between these <i>S. aureus</i> 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 <i>S. aureus</i>, involved in the biosynthesis of lantibiotics, was acquired <i>via</i> horizontal gene transfer from environmental bacteria. Comparisons of the gene abundance profiles in 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 <i>S. aureus</i>, with significant implications for clinical microbiology.IMPORTANCEOur study uncovers significant genomic variations in <i>Staphylococcus aureus</i> strains associated with atopic dermatitis. We observed adaptive evolution tailored to the disease microenvironment, characterized by a smaller pan-genome than strains from healthy skin both on the global and local levels. Key functional categories driving strain diversification include "replication and repair" and "transporters," with transposases being pivotal. Interestingly, the local strains predominantly featured metal-related genes, whereas global ones emphasized antimicrobial resistances, signifying scale-dependent diversification nuances. We also pinpointed horizontal gene transfer events, indicating interactions between human-associated and environmental bacteria. These insights expand our comprehension of <i>S. aureus</i>'s genetic adaptation in atopic dermatitis, yielding valuable implications for clinical approaches.