Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Drug Resistance

Background:

• Staphylococcus aureus causes persistent infections due to antibiotic-tolerant persister cells.
• Phenol-soluble modulins (PSMs) are virulence factors that can reduce persister cell formation.
• PSMs can form amyloid-like fibrils, potentially influencing their function.

Purpose of the Study:

• To investigate the individual and combined effects of synthetic PSMα peptides and their amyloid-like fibrils on S. aureus persister cells.
• To determine the role of soluble versus fibrillated PSMs in reducing antibiotic tolerance.
• To evaluate PSM activity in a persister-cell-hyperforming mutant and in biofilms.

Main Methods:

• Treatment of ciprofloxacin-selected S. aureus persister cells with synthetic PSMα peptides and their fibrillated forms.
• Assessment of persister cell frequency across different growth phases.
• Testing peptide efficacy in a Krebs cycle mutant and in biofilm models.

Main Results:

• PSMα2 and a mixture of all four PSMα peptides reduced persister frequency, with activity dependent on the soluble peptide form.
• Fibrillated peptides showed no effect on persister cells.
• PSMα4 and peptide combinations were most effective in a persister-hyperforming mutant; only the peptide combination reduced persisters in biofilms.

Conclusions:

• Individual PSMα peptides and their combinations contribute to reducing S. aureus persister cells, with soluble forms being crucial.
• Fibrillated PSMs are inactive against persister cells, suggesting structural conformation is key to function.
• Further research is needed to elucidate the biological role of PSMs in combating antibiotic tolerance.