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Abstract
<p class="first" id="P1">The heterogeneous course, severity, and treatment responses
among patients with atopic
dermatitis (AD; eczema) highlight the complexity of this multifactorial disease. Prior
studies have used traditional typing methods on cultivated isolates or sequenced a
bacterial marker gene to study the skin microbial communities of AD patients. Shotgun
metagenomic sequence analysis provides much greater resolution, elucidating multiple
levels of microbial community assembly ranging from kingdom to species and strain-level
diversification. Here, we analyze microbial temporal dynamics from a cohort of pediatric
AD patients sampled throughout the disease course. Species-level investigation of
AD flares showed greater
<i>Staphylococcus aureus</i>-predominance in patients with more severe disease and
<i>S. epidermidis</i>-predominance in patients with less severe disease. At the strain-level,
metagenomic
sequencing analyses demonstrated clonal
<i>S. aureus</i> strains in more severe patients and heterogeneous
<i>S. epidermidis</i> strain communities in all patients. To investigate strain-level
biological effects
of
<i>S. aureus</i>, we topically colonized mice with strains isolated from AD patients
and controls.
This cutaneous colonization model demonstrated
<i>S. aureus</i> strain-specific differences in eliciting skin inflammation and immune
signatures
characteristic of AD patients. Specifically,
<i>S. aureus</i> isolates from AD patients with more severe flares induced epidermal
thickening and
expansion of cutaneous Th2 and Th17 cells. Integrating high-resolution sequencing,
culturing, and animal models demonstrated how functional differences of staphylococcal
strains may contribute to the complexity of AD disease.
</p>