Staphylococcus aureus phenol soluble modulin aggregation kinetics

The infective ability of the opportunistic pathogen Staphylococcus aureus,
recognized as the most frequent cause of biofilm-associated infections, is
associated with biofilm mediated resistance to host immune response.
Phenol-soluble modulins (PSM) comprise the structural scaffold of S.
aureus biofilms through self-assembly into functional amyloids, but the
role of individual PSMs during biofilm formation remains poorly understood
and the molecular pathways of PSM self-assembly have yet to be identified.
Here, we demonstrate high degree of cooperation between individual PSMs
during functional amyloid formation. PSMα3 initiates the aggregation,
forming unstable aggregates capable of seeding other PSMs resulting in
stable amyloid structures. Using chemical kinetics we dissect the
molecular mechanism of aggregation of individual PSMs showing that PSMα1,
PSMα3 and PSMβ1 display secondary nucleation whereas PSMβ2 aggregates
through primary nucleation and elongation. Our findings suggest that the
various PSMs have evolved to ensure fast and efficient biofilm formation
through cooperation between individual peptides.