Streptococcus in the skin microbiome of children exacerbates inflammation in atopic dermatitis

Summary: Abstract Body: The microbiome in pediatric atopic dermatitis (AD) is unique, containing a marked increase in Streptococcus (Strep) species compared to adults. To better understand this microbial community and its influences on disease, swabs from multiple skin sites were collected from children under 6yo with AD (N=19) and age-matched healthy controls (N=16). Shotgun metagenomics and live culture measurements confirmed a higher abundance of Strep in children than adults and more Strep was found on lesional skin than nonlesional skin (P=0.0071). Furthermore, there was a strong correlation between the abundance of live Strep species, S. aureus, and disease severity (P=0.0036). To understand if Strep-S. aureus coexistence affects the skin barrier, conditioned media (CM) from strains of S. aureus and Strep oralis (a dominant species on children’s skin) was added to human keratinocytes. Minimal cytotoxicity was seen if CM from each species was added alone (LDH release =10.7% for 5% S. aureus CM and 1.0% for 15% S. oralis CM), but when as little as 15% CM from S. oralis was added to 5% S. aureus CM, LDH release rose to 62.2%, indicating a strong synergistic cytotoxic effect. This synergy also directly exacerbated inflammation in a mouse model of AD (MC903), where application of both S. aureus and S. oralis each at 5x105 CFU/cm2 intensified skin barrier disruption and type 2 inflammation compared to applying either species alone at 1x106 CFU/cm2 (P=0.028). S. aureusstrains lacking phenol-soluble module-α or δ-toxin did not synergize with Strep, and skin inflammation was blocked by a novel antimicrobial strain of Staph hominis (ShC2) that kills both S. aureus and Strep, while a mutant strain of ShC2 lacking the active lantibiotic (ShC2-Δlanti) did not. These findings reveal a previously unknown cooperation between S. aureus and Strep, suggesting that synergy and competition between bacteria likely play an important role in the pathophysiology of AD in children. Teruaki Nakatsuji¹, Yang Chen¹, Sydney Dong¹, Alexander Horswill², George Hightower¹, Richard L. Gallo¹ 1. Dermatology, University of California San Diego, La Jolla, CA, United States. 2. Immunolody and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States. Innate Immunity, Microbiology, and Microbiome