S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection

Area of Science:

• Dermatology
• Microbiology
• Immunology

Background:

• Individuals with atopic dermatitis (AD) exhibit high colonization rates of *Staphylococcus aureus* and increased susceptibility to severe viral infections.
• *S. aureus* secreted virulence factors are hypothesized to compromise keratinocyte biology, leading to enhanced viral susceptibility through skin barrier disruption, impaired differentiation, and inflammation.

Purpose of the Study:

• To investigate the role of *S. aureus* virulence factors in altering keratinocyte biology and increasing susceptibility to viral infections.
• To identify specific virulence factors responsible for these effects and elucidate potential mechanisms, including the role of SEIQ and CD40.

Main Methods:

• Human keratinocytes were exposed to conditioned media from various *S. aureus* strains (USA300, HG003, RN4220) or purified virulence factors.
• Assessed keratinocyte susceptibility to vaccinia virus infection, barrier function, and differentiation markers (qPCR).
• Utilized CRISPR/Cas9 to knock out CD40 in keratinocytes to evaluate its role in SEIQ-mediated responses.

Main Results:

• Exposure to USA300 conditioned media or purified staphylococcal enterotoxin-like Q (SEIQ) significantly increased keratinocyte susceptibility to vaccinia virus infection.
• SEIQ significantly decreased skin barrier function and altered keratinocyte differentiation.
• CD40 knockout on keratinocytes did not abolish SEIQ-mediated proinflammatory cytokine expression or barrier function impairment.

Conclusions:

• Specific *S. aureus* virulence factors, particularly SEIQ, enhance epidermal cell susceptibility to viral infections.
• SEIQ contributes to compromised skin barrier function and altered keratinocyte differentiation, potentially explaining increased cutaneous viral infections in atopic dermatitis.
• CD40 is not essential for SEIQ's effects on keratinocytes, suggesting alternative receptors mediate its actions.