Solution Structures of Phenol-Soluble Modulins α1, α3, and β2, Virulence Factors from Staphylococcus aureus

Phenol-soluble modulins (PSMs) are peptide virulence factors produced by staphylococci. These peptides contribute to the overall pathogenicity of these bacteria, eliciting multiple immune responses from host cells. Many of the a-type PSMs exhibit cytolytic properties and are able to lyse particular eukaryotic cells, including erythrocytes, neutrophils, and leukocytes. In addition, they also appear to contribute to the protection of the bacterial cell from the host immune response through biofilm formation and detachment. In this study, three of these peptide toxins, PSMs alpha 1, alpha 3, and beta 2, normally produced by Staphylococcus aureus, have been synthesized using solid-supported peptide synthesis (SPPS) (PSM alpha 1 and PSM alpha 3) or made by heterologous expression in Escherichia coli (PSM beta 2). Their three-dimensional structures were elucidated using nuclear magnetic resonance spectroscopy. PSM alpha 1 and PSM alpha 3 each consist of a single amphipathic helix with a slight bend near the N- and C-termini, respectively. PSM beta 2 contains three amphipathic helices, which fold to produce a v-like shape between alpha-helix 2 and alpha-helix 3, with alpha-helix 1 folded over such that it is perpendicular to alpha-helix 3. The availability of three-dimensional structures permits spatial analysis of features and residues proposed to control the biological activity of these peptide toxins.