Differential fibril morphologies and thermostability determine functional roles of Staphylococcus aureus PSM$α$1 and PSM$α$3

Rayan, Bader; Upcher, Alexander; Barnea, Eilon; Khokhlov, Alexander; Landau, Meytal

doi:10.3389/fmolb.2023.1184785

Journal Article

PUBDB-2023-06862

Differential fibril morphologies and thermostability determine functional roles of Staphylococcus aureus PSM$α$1 and PSM$α$3

Rayan, B. ; Barnea, E. ; Khokhlov, A. ; Upcher, A. ; Landau, M. (Corresponding author)CSSB*EMBL*DESY*

2023
Frontiers Lausanne

Frontiers in molecular biosciences 10, 1184785 (2023) [10.3389/fmolb.2023.1184785]

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Please use a persistent id in citations: doi:10.3389/fmolb.2023.1184785 doi:10.3204/PUBDB-2023-06862

Abstract: Phenol-soluble modulins (PSMs) are virulent peptides secreted by staphylococci that undergo self-assembly into amyloid fibrils. This study focuses on Staphylococcus aureus PSMα1 and PSM$α$3, which share homologous sequences but exhibit distinct amyloid fibril structures. Upon subjecting PSMα1 to an 80°C heat shock, it fibrillates into cross-β structures, resulting in the loss of cytotoxic activity. Conversely, PSM$α$3 cross-α fibrils undergo reversible disaggregation upon heat shock, leading to the recovery of cytotoxicity. The differential thermostability probably arises from the presence of hydrogen bonds along the β-strands within the β-sheets of the cross-β fibrils. We propose that the breakdown of PSM$α$3 fibrils into soluble species, potentially co-aggregating with membrane lipids, is crucial for its toxic process and enables the reversible modulation of its biological activity under stress conditions. In contrast, the formation of robust and irreversible cross-β fibrils by PSM$α$1 corresponds to its role in biofilm stability. These findings emphasize how the unique fibril morphologies and thermostability of PSMα1 and PSM$α$3 shape their functional roles in various environments of S. aureus.

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