Heparin promotes fibrillation of most phenol soluble modulin peptides from S. aureus: a possible strengthening of the bacterial biofilm

Phenol soluble modulins (PSMs) are virulence peptides secreted by different Staphylococcus aureus strains. In addition, PSMs are able to form amyloid fibrils which may strengthen the biofilm matrix. The highly sulfated glycosaminoglycan heparin promotes S.aureus infection but the basis for this is unclear. We hypothesized that heparin promotes PSM fibrillation and in this way aids bacterial colonization. Here we address this hypothesis using a combination of different biophysical techniques along with peptide microarrays. We find that heparin accelerates fibrillation of all -PSMs (except PSM2) and {delta}-toxin, but inhibits {beta}-PSMs fibrillation by blocking nucleation. Given that S. aureus secretes higher levels of -PSMs than {beta}-PSMs peptidess, heparin is likely to overall promote fibrillation. Heparin binding is driven by multiple positively charged lysine residues in -PSMs and {delta}-toxins, whose removal strongly reduces affinity. Binding of heparin does not alter the final fibril conformation. Rather, heparin provides a scaffold to catalyze or inhibit fibrillation. Our findings suggest that heparin may strengthen bacterial biofilm through increased PSM fibrillation. O_FIG O_LINKSMALLFIG WIDTH=184 HEIGHT=200 SRC="FIGDIR/small/434294v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@99c3bdorg.highwire.dtl.DTLVardef@101d9b6org.highwire.dtl.DTLVardef@7c4058org.highwire.dtl.DTLVardef@1647eca_HPS_FORMAT_FIGEXP M_FIG C_FIG