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 solved to ensure fast and efficient biofilm formation through cooperation between individual peptides.
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2 and 4 in addition to Supplementary Figure 1-5 and 7 and 8.
Staphylococcus aureus Phenol soluble modulin aggregation kineticsDryad Digital Repository, doi:10.5061/dryad.w6m905qmx.
- Maria Andreasen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Manajit Hayer-Hartl, Max Planck Institute of Biochemistry, Germany
© 2020, Zaman & Andreasen
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