Erratum for Syed et al., Staphylococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation

Phenol-soluble modulins α are major virulence factors of Staphylococcus aureus secretome promoting inflammatory response in human epidermis

“…The amounts of PSM α3 and N-formylated PSM α3 produced were approximately 56 µM and 31 µM respectively, as determined by assay in LC-ESI-MS. As this study was focused on the effect of α-type PSMs on epidermis, stimulation of primary human keratinocytes with purified PSM Fα3 and PSM α3 were performed to evaluate a potential biological effect of formylation on skin inflammation as has been previously reported for neutrophil chemotaxis [ 21 ]. In addition, a synthetic N-formylated PSM α3 was used as a standard because PSM α3 was previously shown to be the most lytic and pro-inflammatory PSM on various cell types [ 17 , 26 ].…”

“…In clinical S. aureus strains responsible for persistent bacteremia, high expression of α-type and β-type PSMs was observed and was correlated with neutrophil lysis and enhanced S. aureus survival [ 46 ]. In human keratinocytes, synthetic PSMs α1-4 and δ-toxin induce significant lysis at a high concentration, PSM α3 being the most potent and leading to the death of almost all cells [ 26 ]. This study investigated the role of lower concentrations of PSM α3 in the alteration of human primary keratinocyte viability.…”

“…Nevertheless, using supernatants from PSM-deficient strains, deletion of only α-type PSMs did not completely abrogate the observed cytotoxic effect as compared to deletion of all PSMs, a finding suggesting synergistic action of α-type PSMs with other PSMs on keratinocyte viability alteration. While previous studies excluded a role of PSMs β in decreased keratinocyte viability, δ-toxin has been reported to be highly cytotoxic and may play a concomitant role with α-type PSMs in keratinocyte damage [ 26 , 33 ]. Among the S. aureus secreted factors, our results highlighted the major effect of PSMs on keratinocyte viability, acting as potent cytotoxins.…”

“…At high concentrations, PSMs are able to induce lysis of neutrophils, erythrocytes, mastocytes and keratinocytes by forming pores in the cell membrane [ 17 , 25–27 ]. Whatever the cell type, PSM α3, appears to be the most potent [ 17 , 26 ]. PSM α3 is able to form cross-α fibrils, which co-aggregate with the cell membrane, resulting in membrane rupture and T cell death [ 28 ].…”

“…Among PSMs, PSM α3 has the most potent pro-inflammatory activity in neutrophils [ 17 , 21 , 32 ]. Recently, the immunomodulatory properties of α-type PSMs were studied in keratinocytes and on murine models.At a lytic concentration, PSMs are critical in stimulating the release of the pro-inflammatory cytokines IL-18 and IL-1β from human keratinocytes, PSM α3 being the most efficient inducer [ 26 ]. In a mouse model of S. aureus epicutaneous infection, α-type PSMs were critical in inducing an IL-17-mediated skin inflammatory response associated with epidermal thickening and neutrophil infiltration [ 33 ].…”