Biphasic influence of Staphylococcus aureus on human epidermal tight junctions

Area of Science:

• Dermatology
• Microbiology
• Cell Biology

Background:

• Bacterial infections, particularly Staphylococcus aureus, pose risks to compromised skin barriers like in atopic dermatitis.
• Previous studies indicated Staphylococcus aureus impacts tight junction (TJ) proteins and impairs TJ function in HaCaT cells.
• Functional studies in more relevant human skin models were lacking.

Purpose of the Study:

• To investigate Staphylococcus aureus colonization and infection effects on TJ barrier function in primary human keratinocytes and reconstructed human epidermis (RHE).
• To elucidate the short-term and long-term impacts of S. aureus on skin barrier integrity and TJ protein localization.

Main Methods:

• Infection of primary human keratinocytes and reconstructed human epidermis (RHE) with live Staphylococcus aureus.
• Analysis of tight junction (TJ) barrier function, occludin phosphorylation, and localization of TJ proteins (occludin, claudin-1, claudin-4).
• Investigation of the role of the S. aureus agr regulon and proinflammatory cytokines.

Main Results:

• Short-term S. aureus inoculation increased TJ barrier function in human cells, associated with occludin phosphorylation and membrane localization of occludin and claudin-4.
• Long-term incubation led to decreased claudin-1 and claudin-4 at cell membranes and impaired TJ barrier function.
• The S. aureus agr regulon influenced the initial TJ enhancement, while proinflammatory cytokines affected both phases.

Conclusions:

• Staphylococcus aureus exhibits a dual effect on the skin's TJ barrier: a short-term protective enhancement followed by long-term disruption.
• These findings highlight the complex interaction between S. aureus and human skin barrier function, with implications for conditions like atopic dermatitis.