Extreme amyloid polymorphism in Staphylococcus aureus virulent PSMa peptides
Members of the Staphylococcus aureus phenol soluble modulin (PSM) peptide family are secreted as functional amyloids that serve diverse roles in pathogenicity and may be present as full length peptides or as naturally occurring truncations. We recently showed that the activity of PSMa3, the most toxic member, stems from the formation of cross a fibrils, which are at variance with the cross b fibrils linked with eukaryotic amyloid pathologies. Here, we show that PSMa1 and PSMa4, involved in biofilm structuring, form canonical cross b amyloid fibrils wherein b sheets tightly mate through steric zipper interfaces, conferring high stability. Contrastingly, a truncated PSMa3 has antibacterial activity, forms reversible fibrils, and reveals two polymorphic and atypical b rich fibril architectures. These architectures are radically different from both the cross a fibrils formed by full length PSMa3, and from the canonical cross b fibrils. Our results point to structural plasticity being at the basis of the functional diversity exhibited by S. aureus PSMas.The phenol soluble modulin PSMa3 secreted by Staphylococcus aureus forms cross a amyloid like fibrils. Here the authors reveal the amyloid polymorphism of PSMs by presenting the cross b amyloid fibril structures of the biofilm associated PSMa1 and PSMa4 and showing that truncated PSMa3 antibacterial peptides form distinct out of register b sheets and a polymorph with a hexameric architecture of b sheets.
Nature Communications