Fig. 7.

Proposed model of cell aggregation and ECM stabilization mediated by moonlighting virulence factors and ribosomal proteins in S. aureus biofilms. Biofilms cultivated in a continuous flow system on a silicon tube surface grow to high cell densities, which leads to oxygen limitation. Consequently, biofilm-embedded cells are driven toward anaerobic metabolism and secrete high amounts of fermentation products lowering the local pH within the ECM. Furthermore, S. aureus biofilm cells release high amounts of eDNA, virulence factors and ribosomal proteins (besides other cytoplasmic proteins). These proteins get protonated in the acidic ECM environment because of their alkaline character. The accumulation of these cationic proteins, eDNA and anionic fermentation products along with other anionic metabolites (I) creates an electrostatic network involving eDNA and anionic cell surfaces (harboring anionic teichoic acids), which leads to cell aggregation and ECM stabilization and (II) leads to an osmotic stress response in biofilm-embedded cells. ECM = Extracellular matrix.