Direct and synergistic hemolysis caused by Staphylococcus phenol-soluble modulins: implications for diagnosis and pathogenesis

Phenol-soluble modulins are secreted staphylococcal peptides with an amphipathic alpha-helical structure. Some PSMs are strongly cytolytic toward human neutrophils and represent major virulence determinants during Staphylococcus aureus skin and blood infection. However, capacities of PSMs to lyse human erythrocytes have not been investigated. Here, we demonstrate that many S. aureus and Staphylococcus epidermidis PSMs lyse human erythrocytes. Furthermore, synergism with S. aureus beta-toxin considerably increased the hemolytic capacities of several PSMs. This synergism may be of key importance in PSM and beta-toxin-producing S. aureus or in mixed-strain or -species infections with PSM and beta-toxin producers. Of specific interest, several PSMs, in particular PSM alpha peptides, contributed to a considerable extent to synergistic hemolysis with beta-toxin or when using the beta-toxin-producing strain RN4220 in CAMP assays. Thus, CAMP-type assays should not be used to detect or quantify S. aureus delta-toxin production, but may be used for an overall assessment of Agr functionality. Our study suggests an additional role of PSMs in staphylococcal pathogenesis and demonstrates that the repertoire of staphylococcal hemolysins is not limited to S. aureus and is much larger and diverse than previously thought. Published by Elsevier Masson SAS on behalf of Institut Pasteur.