Abstract
ABSTRACTThe bacterial pathogen Staphylococcus aureus plays an important role in atopic dermatitis (AD), a chronic disorder that mostly affects children. Colonization of the skin of AD patients by S. aureus exacerbates the disease, but the molecular determinants of the bacterium-skin adhesive interactions are poorly understood. Specifically, reduced levels of natural moisturizing factor (NMF) in the stratum corneum have been shown to be associated with more severe AD symptoms, but whether this is directly related to S. aureus adhesion is still an open question. Here, we demonstrate a novel relationship between NMF expression in AD skin and strength of bacterial adhesion. Low-NMF corneocytes, unlike high-NMF ones, are covered by a dense layer of nanoscale villus protrusions. S. aureus bacteria isolated from AD skin bind much more strongly to corneocytes when the NMF level is reduced. Strong binding forces originate from a specific interaction between the bacterial adhesion clumping factor B (ClfB) and skin ligands. Remarkably, mechanical tension dramatically strengthens ClfB-mediated adhesion, as observed with catch bonds, demonstrating that physical stress plays a role in promoting colonization of AD skin by S. aureus. Collectively, our findings demonstrate that patient NMF levels regulate the strength of S. aureus-corneocyte adhesion, the first step in skin colonization, and suggest that the ClfB binding mechanism could represent a potential target for new therapeutic treatments.
Highlights
IMPORTANCE Bacterium-skin interactions play important roles in skin disorders, yet their molecular details are poorly understood
These results demonstrate that natural moisturizing factor (NMF) levels in atopic dermatitis (AD) skin control the strength of S. aureus adhesion, which may explain why this factor is important in determining the severity of the AD disease
Bacterium-skin adhesion plays an important role in skin disorders, yet the molecular interactions involved have long been inaccessible to study
Summary
IMPORTANCE Bacterium-skin interactions play important roles in skin disorders, yet their molecular details are poorly understood. We identify a unique relationship between the level of natural moisturizing factor (NMF) in the skin and the strength of bacterium-corneocyte adhesion. The mechanisms through which FLG mutations and/or low NMF facilitate or enhance adhesion and colonization behavior of S. aureus are not known. Clarification of this issue may give us new clues to develop therapeutics to reduce skin colonization and infection. Strong adhesion forces originate from DLL binding of ClfB to corneocyte ligands and are activated by mechanical force These results demonstrate that NMF levels in AD skin control the strength of S. aureus adhesion, which may explain why this factor is important in determining the severity of the AD disease. By helping to define the bacterial and host factors contributing to bacterial adhesion to skin, this emerging nanotechnology offers promise for identifying new agents to reduce— or prevent—skin colonization by S. aureus
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