Abstract
Several members of the staphylococcal phenol-soluble modulin (PSM) peptide family exhibit pronounced capacities to lyse eukaryotic cells, such as neutrophils, monocytes, and erythrocytes. This is commonly assumed to be due to the amphipathic, α-helical structure of PSMs, giving PSMs detergent-like characteristics and allowing for a relatively non-specific destruction of biological membranes. However, the capacities of PSMs to lyse synthetic phospholipid vesicles have not been investigated. Here, we analyzed lysis of synthetic phosphatidylcholine (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC) vesicles by all Staphylococcus aureus and S. epidermidis PSMs. In addition, we investigated the lytic capacities of culture filtrates obtained from different S. aureus PSM deletion mutants toward POPC vesicles. Our results show that all staphylococcal PSMs have phospholipid vesicle-lysing activity and the capacity of S. aureus culture filtrate to lyse POPC vesicles is exclusively dependent on PSMs. Notably, we observed largely differing capacities among PSM peptides to lyse POPC vesicles. Interestingly, POPC vesicle-lytic capacities did not correlate with those previously seen for the lysis of eukaryotic cells. For example, the β-type PSMs were strongly lytic for POPC vesicles, but are known to exhibit only very low lytic capacities toward neutrophils and erythrocytes. Thus our results also suggest that the interaction between PSMs and eukaryotic membranes is more specific than previously assumed, potentially depending on additional structural features of those membranes, such as phospholipid composition or yet unidentified docking molecules.
Highlights
Many members of the genus Staphylococcus are important human pathogens
To analyze whether and to which degree phenol-soluble modulin (PSM) peptides lyse POPC vesicles, we set up a fluorescein release assay
S. aureus PSM peptides lysed the POPC vesicles when applied at 0.5 μM final concentration in the order PSMβ1 > PSMβ2 > PSMα4 > PSMα1 > PSMα3 > PSMα2 > δ-toxin (Figure 2)
Summary
Many members of the genus Staphylococcus are important human pathogens. Staphylococcus aureus in particular causes a multitude of frequently severe and life-threatening diseases, with acute disease promoted by a series of secreted toxins and other virulence determinants [1]. Less virulent hospital-associated strains characteristically produce smaller amounts of those peptide toxins [6] In addition to their cytolytic potential, PSM peptides promote inflammatory responses by activating the FPR2 receptor [7]. They contribute to biofilm structuring, detachment, and the systemic dissemination of biofilm-associated infection [8,9]. This indicates that the interaction of PSMs with eukaryotic membranes is governed by more complex interactions than previously believed The elucidation of such interactions will be an important task of future investigations aimed to answer the key question of why eukaryotic cells are much more susceptible to PSM cytolytic activity than bacterial cells
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