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S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection
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DOI：10.1128/spectrum.01684-23.png)
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Abstract
En 中文
Individuals with atopic dermatitis (AD) are highly colonized by Staphylococcus aureus and are more susceptible to severe viral complications. We hypothesized that S. aureus secreted virulence factors may alter keratinocyte biology to enhance viral susceptibility through disruption of the skin barrier, impaired keratinocyte differentiation, and/or inflammation. To address this hypothesis, human keratinocytes were exposed to conditioned media from multiple S. aureus strains that vary in virulence factor production (USA300, HG003, and RN4220) or select purified virulence factors. We have identified the S. aureus enterotoxin-like superantigen SElQ, as a virulence factor of interest, since it is highly produced by USA300 and was detected on the skin of 53% of AD subjects (n = 72) in a study conducted by our group. Treatment with USA300 conditioned media or purified SElQ resulted in a significant increase in keratinocyte susceptibility to infection with vaccinia virus, and also significantly decreased barrier function. Importantly, we have previously demonstrated that keratinocyte differentiation influences susceptibility to viral infection, and our qPCR observations indicated that USA300 S. aureus and SElQ alter differentiation in keratinocytes. CRISPR/Cas9 was used to knock out CD40, a potential enterotoxin receptor on epithelial cells. We found that CD40 expression on keratinocytes was not completely necessary for SElQ-mediated responses, as measured by proinflammatory cytokine expression and barrier function. Together, these findings support that select S. aureus virulence factors, particularly SElQ, enhance the susceptibility of epidermal cells to viral infection, which may contribute to the increased cutaneous infections observed in individuals with AD.
Keywords:
Staphylococcus aureus
atopic dermatitis
keratinocytes
viral infection
superantigens
barrier function
vaccinia virus
USA300
CD40
SElQ
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