Staphylococcus aureus surface attachment selectively influences tolerance against charged antibiotics

Area of Science:

• Microbiology
• Biomaterials Science
• Infectious Diseases

Background:

• Surgical site infections are a significant risk during implant placement.
• Prophylactic antibiotics can promote bacterial resistance and persistent infections.
• Understanding early bacterial adaptation to surfaces is crucial for improving prophylaxis.

Purpose of the Study:

• To investigate the molecular mechanisms of Staphylococcus aureus adaptation to medical-grade titanium surfaces.
• To determine how these adaptations affect antibiotic tolerance during early attachment.
• To identify potential targets for novel anti-infective strategies in implant surgery.

Main Methods:

• Gene expression analysis to identify upregulated cellular systems in S. aureus.
• Synchrotron-sourced attenuated total reflection Fourier-transform infrared microspectroscopy to analyze cell surface biomolecular properties.
• Assessment of S. aureus tolerance to vancomycin and cefazolin following surface attachment.

Main Results:

• S. aureus upregulates systems for d-alanylation of teichoic acids and lysylation of phosphatidylglycerol upon titanium attachment.
• These modifications alter the cell surface charge, increasing tolerance to positively charged vancomycin.
• No significant change in tolerance was observed for the negatively charged antibiotic cefazolin.

Conclusions:

• S. aureus employs specific physiological adaptations to enhance antibiotic tolerance during early surface colonization.
• The observed changes in cell surface charge are key to increased vancomycin tolerance.
• Findings can guide rational antibiotic selection for prophylaxis and suggest targets for new anti-infective therapies.