Biofilm Propensity of Staphylococcus Aureus Skin Isolates Is Associated With Increased Atopic Dermatitis Severity and Barrier Dysfunction in the MPAACH Pediatric Cohort

Abstract

Atopic dermatitis (AD) patients are commonly colonized with Staphylococcus aureus, and staphylococcal biofilms have been described in adult AD lesions. The commensal Staphylococcus epidermidis can antagonize S aureus, but its role in AD is unclear. These investigators sought to characterize S aureus and S epidermidis colonization and biofilm propensity and determine their association with AD severity, barrier function, and epidermal gene expression in an early-life cohort of children with AD.The Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort consists of children aged 1 to 2 years in the greater Cincinnati, Ohio area with either physician-diagnosed AD or a positive parental response to all 3 questions on the Children’s Eczema Questionnaire.A total of 500 children are being enrolled. The current study was focused on the first 400 MPAACH participants. Demographic, environmental, asthma trigger, and personal and family allergy and asthma history data were compiled. AD severity was documented with the Scoring of Atopic Dermatitis scale. Topical medications were withheld the night before the visit. The biofilm propensity of staphylococcal isolates was assessed by crystal violet assays. Gene expression of filaggrin and antimicrobial alarmins S100A8 and S100A9 were measured in keratinocyte RNA extracted from skin tape strips. Staphylococcal biofilms were visualized with scanning electron microscopy.Among the entire 400 children, 26.5% had positive cultures for S aureus, whereas 71% were positive for S epidermidis. A total of 62% of staphylococcal isolates formed moderate or strong biofilms, whereas 68% of those co-colonized with both staphylococcal species exhibited strains that formed cooperative mixed-species biofilms. Scanning electron microscopy verified presence of biofilms. S aureus strains showing higher relative biofilm propensity compared with S epidermidis were associated with increased AD severity and increased lesional and nonlesional transepidermal water loss. Biofilm propensity was associated with decreased FLG expression, which otherwise encodes filaggrin, a structural protein essential to prevent water loss.Collectively, these data suggest that, although S. aureus colonization is associated with increased AD severity, it is the ability of S. aureus to form strong biofilms and the balance between biofilm-forming S. aureus and S epidermidis strains that are particularly important factors affecting AD severity and barrier dysfunction.Biofilms are important in many complex disease processes, and atopic dermatitis appears to be no exception. Whether through genetic (eg, allergy and filaggrin mutations), environmental, or other factors, the altered skin barrier predisposes to S aureus colonization. This jibes with the common clinical observation that acute AD flares are often responsive to a course of both systemic and topical antistaphylococcal therapy while aggressively employing moisturizing measures.