Mechanical Forces Guiding Staphylococcus aureus Cellular Invasion.

Area of Science:

• Microbiology
• Biophysics
• Cell Biology

Background:

• Staphylococcus aureus invades mammalian cells, evading immune defenses and antibiotics.
• Cellular invasion is mediated by bacterial fibronectin-binding proteins (FnBPA, FnBPB) and host α5β1 integrins.
• The role of extracellular matrix protein fibronectin (Fn) as a bridge and the forces involved are not fully understood.

Purpose of the Study:

• To investigate the molecular forces governing Staphylococcus aureus cellular invasion.
• To elucidate the FnBPA-Fn-integrin interaction mechanism.
• To understand the role of protein mechanobiology in bacterial adhesion and host cell invasion.

Main Methods:

• Single-cell and single-molecule experiments.
• Analysis of the FnBPA-Fn-integrin interaction.
• Investigating Fn-dependent adhesion dynamics between S. aureus and endothelial cells.

Main Results:

• FnBPA mediates strong adhesion to soluble Fn (~1500 pN) via a tandem β-zipper.
• The FnBPA-Fn complex binds α5β1 integrins with significantly higher strength than classical Fn-integrin bonds (~100 pN).
• Fn binding to FnBPA allosterically activates cryptic integrin-binding sites, enhancing adhesion.

Conclusions:

• Protein mechanobiology and allosteric activation are crucial for S. aureus host cell invasion.
• Fn-dependent adhesion strengthens over time, indicating rapid internalization (minutes).
• Findings provide a molecular basis for S. aureus invasion and suggest therapeutic strategies against intracellular pathogens.