Internalization of Staphylococcus aureus by human keratinocytes

Area of Science:

• Microbiology
• Cell Biology
• Infectious Diseases

Background:

• Staphylococcus aureus is a significant human pathogen causing diverse infections.
• Bacterial internalization by host cells like keratinocytes can lead to chronic infections and dissemination.
• Understanding S. aureus internalization mechanisms is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the mechanisms by which Staphylococcus aureus is internalized by keratinocytes.
• To identify the bacterial and host cell factors involved in S. aureus uptake.
• To explore potential alternative pathways for S. aureus internalization.

Main Methods:

• Co-culturing immortalized and primary keratinocytes with Staphylococcus aureus isogenic mutants lacking fibronectin-binding proteins (FnBPs).
• Utilizing a recombinant protein of the S. aureus FnBP fibronectin-binding domain.
• Employing an anti-alpha5beta1 antibody to block integrin-mediated uptake.
• Assessing the role of S. aureus clumping factor B (ClfB) in keratinocyte internalization.

Main Results:

• Internalization of S. aureus by immortalized keratinocytes depends on bacterial FnBPs and host alpha5beta1 integrin.
• Primary keratinocytes internalize S. aureus via both FnBP-dependent and FnBP-independent pathways.
• S. aureus clumping factor B (ClfB) was not implicated in keratinocyte uptake.
• An alternative S. aureus uptake pathway, independent of FnBPs and alpha5beta1, was identified.

Conclusions:

• Staphylococcus aureus utilizes distinct internalization mechanisms in different keratinocyte types.
• The discovery of FnBP- and alpha5beta1-independent pathways has significant therapeutic implications.
• Targeting bacterial uptake mechanisms could offer novel strategies for treating S. aureus infections.