Extreme amyloid polymorphism in Staphylococcus aureus virulent PSMα peptides

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Staphylococcus aureus phenol-soluble modulin (PSM) peptides are secreted as functional amyloids.
• PSMs play roles in pathogenicity and can exist as full-length peptides or truncations.
• Full-length PSMα3 forms toxic cross-α fibrils, distinct from eukaryotic cross-β amyloid fibrils.

Purpose of the Study:

• To investigate the fibril structures formed by other PSMα peptides (PSMα1, PSMα4) and truncated PSMα3.
• To understand the relationship between PSM structure, stability, and function.
• To explore the structural basis for the functional diversity of S. aureus PSMα peptides.

Main Methods:

• Structural analysis of amyloid fibrils formed by PSMα1, PSMα4, and truncated PSMα3.
• Characterization of fibril architectures, including cross-β and atypical β-rich structures.
• Assessment of fibril stability and functional activities (e.g., antibacterial, biofilm structuring).

Main Results:

• PSMα1 and PSMα4 form stable, canonical cross-β amyloid fibrils via steric zipper interfaces.
• Truncated PSMα3 exhibits antibacterial activity and forms reversible, polymorphic, atypical β-rich fibril architectures.
• These atypical fibril architectures differ significantly from cross-α and canonical cross-β fibrils.

Conclusions:

• S. aureus PSMα peptides display remarkable structural plasticity in their amyloid fibril formation.
• This structural diversity contributes to the varied functional roles of PSMα peptides in S. aureus.
• Understanding PSM amyloid structures offers insights into bacterial pathogenesis and potential therapeutic targets.