<i>Staphylococcus</i> Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development

Abstract

Atopic dermatitis (AD) is commonly associated with colonization by <i>Staphylococcus aureus</i> in the affected skin. To understand the role of <i>S. aureus</i> in the development of AD, we performed whole-genome sequencing of <i>S. aureus</i> strains isolated from the cheek skin of 268 Japanese infants 1 and 6 months after birth. About 45% of infants were colonized with <i>S. aureus</i> at 1 month regardless of AD outcome. In contrast, skin colonization by <i>S. aureus</i> at 6 months of age increased the risk of developing AD. Acquisition of dysfunctional mutations in the <i>S. aureus</i> Agr quorum-sensing (QS) system was primarily observed in strains from 6-month-old infants who did not develop AD. Expression of a functional Agr system in <i>S. aureus</i> was required for epidermal colonization and the induction of AD-like inflammation in mice. Thus, retention of functional <i>S. aureus agr</i> virulence during infancy is associated with pathogen skin colonization and the development of AD.