Heterogeneous Regulation of Staphylococcus Aureus by Different Staphylococcus Epidermidis agr Types in Atopic Dermatitis

The skin commensal Staphylococcus epidermidis exhibits a protective role in skin inflammation; however, the exact functions of S. epidermidis and their mechanisms in atopic dermatitis (AD) are not fully understood. Here, whole-genome sequencing was conducted on strains of S. epidermidis isolated from pediatric patients with AD and revealed significant strain-level heterogeneity in functional genes. Specific sequence analysis of S. epidermidis identified four types of accessory gene regulator (agr) according to locus variations in the agr operon, which was consistent with the metagenomic data of the contextual microbiota. The number of S. epidermidis agr type I was slightly decreased among AD isolates, whereas agr type IV was hardly detected in AD isolates. Functional experiments showed that strains of S. epidermidis agr types I and IV, but not types II and III, inhibited the expression of S. aureus agr-mediated virulence factors in vitro, suppressed S. aureus epidermal colonization, and attenuated skin inflammation in a mouse model. The delineation of genome signatures of S. epidermidis at the strain level in AD and the quorum-sensing interference between S. epidermidis agr type IV and S. aureus provide a foundation for the modulation of the skin microbiota and the treatment of AD.