title: Investigating the lytic activity and structural properties of Staphylococcus aureus phenol soluble modulin (PSM) peptide toxins.
abstract: The ubiquitous bacterial pathogen, Staphylococcus aureus, expresses a large arsenal of virulence factors essential for pathogenesis. The phenol-soluble modulins (PSMs) are a family of cytolytic peptide toxins which have multiple roles in staphylococcal virulence. To gain an insight into which specific factors are important in PSM-mediated cell membrane disruption, the lytic activity of individual PSM peptides against phospholipid vesicles and T cells was investigated. Vesicles were most susceptible to lysis by the PSMα subclass of peptides (α1-3 in particular), when containing between 10 and 30mol% cholesterol, which for these vesicles is the mixed solid ordered (so)-liquid ordered (lo) phase. Our results show that the PSMβ class of peptides has little effect on vesicles at concentrations comparable to that of the PSMα class and exhibited no cytotoxicity. Furthermore, within the PSMα class, differences emerged with PSMα4 showing decreased vesicle and cytotoxic activity in comparison to its counterparts, in contrast to previous studies. In order to understand this, peptides were studied using helical wheel projections and circular dichroism measurements. The degree of amphipathicity, alpha-helicity and properties such as charge and hydrophobicity were calculated, allowing a structure-function relationship to be inferred. The degree of alpha-helicity of the peptides was the single most important property of the seven peptides studied in predicting their lytic activity. These results help to redefine this class of peptide toxins and also highlight certain membrane parameters required for efficient lysis.
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK; Department of Biology and Biochemistry, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Maisem
authors.initials: M
authors.lastname: Laabei
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: W David
authors.initials: WD
authors.lastname: Jamieson
authors.affiliation: Department of Biology and Biochemistry, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biology and Biochemistry, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: van den Elsen
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK. Electronic address: a.t.a.jenkins@bath.ac.uk.
authors.forename: A Toby A
authors.initials: AT
authors.lastname: Jenkins
keywords: Liposome; Peptides; Phenol soluble modulin; Staphylococcus aureus; Vesicle