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Abstract
Staphylococcus aureus δ-toxin is a member of the phenol-soluble modulin (PSM) peptide family. PSMs have multiple functions in staphylococcal pathogenesis; for example, they lyse red and white blood cells and trigger inflammatory responses. Compared to other PSMs, δ-toxin is usually more strongly expressed but has only moderate cytolytic capacities. The amino acid sequences of S. aureus PSMs are well conserved with two exceptions, one of which is the δ-toxin allelic variant G10S. This variant is a characteristic of the subspecies S. argenteus and S. aureus sequence types ST1 and ST59, the latter representing the most frequent cause of community-associated infections in Asia. δ-toxin G10S and strains expressing that variant from plasmids or the genome had significantly reduced cytolytic and pro-inflammatory capacities, including in a strain background with pronounced production of other PSMs. However, in murine infection models, isogenic strains expressing the two δ-toxin variants did not cause measurable differences in disease severity. Our findings indicate that the widespread G10S allelic variation of the δ-toxin locus has a significant impact on key pathogenesis mechanisms, but more potent members of the PSM peptide family may overshadow that impact in vivo.
Highlights
Many members of the genus Staphylococcus are important human pathogens
The analysis of available S. aureus genomes, as well as high pressure liquid chromatography/mass spectrometry (HPLC/MS) analysis of many S. aureus culture filtrates that we performed over the years, revealed the presence of two main allelic variants among S. aureus phenol-soluble modulin (PSM) peptides
One is the PSMα 3 variant PSMα 3N22Y that is characteristically present in clonal complex (CC) 30 and on which we reported earlier[21]
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[1,2]. PSMs are short peptides that are under strict regulation by the Agr quorum-sensing system[7] and secreted by a dedicated transporter without a signal peptide[8]. Less virulent hospital-associated strains characteristically produce smaller amounts of those peptide toxins[5,9] In addition to their cytolytic potential, PSM peptides promote inflammatory responses by activating the formyl peptide receptor 2 (FPR2)[10]. Believed to be a large protein, it is a peptide that tends to oligomerize[15,16] It is encoded within RNAIII, the regulatory molecule of the accessory gene regulator (Agr) quorum-sensing system[17]. The δ -toxin is usually the most strongly produced PSM peptide and in many strains by far the most abundant secreted protein[5,8,19]
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