Biomarker Identification, Viral Susceptibility and Management in S. aureus Colonized AD Patients

Project Summary/Abstract
Staphylococcus aureus (S. aureus) has been strongly implicated as a causal factor in pathogenesis of atopic
dermatitis (AD) since the 1970s, and is further supported by publications demonstrating S. aureus skin
colonization precedes AD onset. ADRN studies found that 50% of AD subjects are colonized and this AD
phenotype is associated with greater epidermal barrier dysfunction, type 2 immunity, disease severity and
remarkable alterations in the skin microbiome (increased S. aureus relative abundance and reduced
abundance of the commensal bacteria, Cutibacterium acnes (C. acnes). Additionally, S. aureus-colonized
AD subjects are more likely to develop a severe viral condition, called eczema herpeticum. An even more
serious condition is eczema vaccinatum, caused by exposure to vaccinia virus (smallpox vaccination), which
has a fatality rate as high as 30%. In an effort to explain this, we found discovered that epidermal exposure
to a highly virulent S. aureus strain (USA300), commonly found on AD subjects, markedly enhances its
susceptibility to vaccinia virus. Collectively, these observations support our hypothesis that S. aureus may be
a key driver of disease severity and response to systemic treatments (Aim 1) as well as serious viral
complications (Aim 2). Determining what role C. acnes, the most abundant commensal skin bacteria, plays
in suppressing S. aureus will be the focus of studies outlined in Aim 3. These studies will leverage the wealth
of deeply-phenotyped AD subjects and their biospecimens from previous ADRN studies (ADRN02-Registry,
ADRN06-ADEH and ADRN09-Dupilumab) and those enrolled into URMCs Longitudinal ‘Real-World’ AD
Study. The Aims demonstrate how the focus is first on the systemic features of S. aureus colonization (e.g.
macro level; Aim 1) and moves to the “epidermal (host) – microbiome” interaction (Aim 2) and ultimately to
the microbe-microbe interaction at the skin surface (e.g. micro level; Aim 3).

Grant Number: 5U01AI152011-06
NIH Institute/Center: NIH
Principal Investigator: Lisa Beck