Do amyloid structures formed by Staphylococcus aureus phenol-soluble modulins have a biological function?

Area of Science:

• Microbiology
• Biochemistry
• Structural Biology

Background:

• Phenol-soluble modulins (PSMs) are crucial virulence factors in Staphylococcus species.
• Recent studies proposed that PSM amyloid formation contributes to cytolysis and biofilm stability.

Purpose of the Study:

• To investigate the role of PSM amyloid formation in staphylococcal virulence and biofilm formation.
• To explore alternative mechanisms for PSM-mediated biofilm stability.

Main Methods:

• Electron microscopy and dye-binding assays to detect PSM amyloid formation.
• Comparison of extracellular fibrous material production between wild-type and PSM-deficient strains.
• Assessment of PSM derivatives' propensity to form amyloids and their correlation with cytolytic and pro-inflammatory activities.
• Investigation of PSM interaction with DNA and DNase resistance.

Main Results:

• PSM amyloid formation was confirmed, but no differences in extracellular fibril production were observed between wild-type and PSM-deficient strains.
• No correlation was found between amyloid formation propensity and cytolytic or pro-inflammatory activities.
• PSMs bind non-specifically to DNA, conferring DNase resistance, which explains biofilm stability without amyloid involvement.
• High conservation of PSMalpha3 suggests a critical, potentially unknown, role for its amyloid-forming capacity.

Conclusions:

• PSM amyloid formation appears to have limited relevance for established biological functions like cytolysis and biofilm stability.
• PSM-DNA interactions provide a more plausible explanation for biofilm stabilization.
• The stringent sequence requirements for PSMalpha3 amyloid formation hint at undiscovered functions crucial for staphylococcal biology.