Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus.
Antimicrobial peptides play an important role in host defense against pathogens. Recently, phenol-soluble modulins (PSMs) from Staphylococcus epidermidis (S. epidermidis) were shown to interact with lipid membranes, form complexes, and exert antimicrobial activity. Based on the abundance and innocui...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2796718?pdf=render |
| _version_ | 1811308400641835008 |
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| author | Anna L Cogen Kenshi Yamasaki Jun Muto Katheryn M Sanchez Laura Crotty Alexander Jackelyn Tanios Yuping Lai Judy E Kim Victor Nizet Richard L Gallo |
| author_facet | Anna L Cogen Kenshi Yamasaki Jun Muto Katheryn M Sanchez Laura Crotty Alexander Jackelyn Tanios Yuping Lai Judy E Kim Victor Nizet Richard L Gallo |
| author_sort | Anna L Cogen |
| collection | DOAJ |
| description | Antimicrobial peptides play an important role in host defense against pathogens. Recently, phenol-soluble modulins (PSMs) from Staphylococcus epidermidis (S. epidermidis) were shown to interact with lipid membranes, form complexes, and exert antimicrobial activity. Based on the abundance and innocuity of the cutaneous resident S. epidermidis, we hypothesized that their PSMs contribute to host defense. Here we show that S. epidermidis delta-toxin (PSMgamma) is normally present in the epidermis and sparsely in the dermis of human skin using immunohistochemistry. Synthetic delta-toxin interacted with neutrophil extracellular traps (NETs) and colocalized with cathelicidin while also inducing NET formation in human neutrophils. In antimicrobial assays against Group A Streptococcus (GAS), delta-toxin cooperated with CRAMP, hBD2, and hBD3. In whole blood, addition of delta-toxin exerted a bacteriostatic effect on GAS, and in NETs, delta-toxin increased their killing capacity against this pathogen. Coimmunoprecipitation and tryptophan spectroscopy demonstrated direct binding of delta-toxin to host antimicrobial peptides LL-37, CRAMP, hBD2, and hBD3. Finally, in a mouse wound model, GAS survival was reduced (along with Mip-2 cytokine levels) when the wounds were pretreated with delta-toxin. Thus, these data suggest that S. epidermidis-derived delta-toxin cooperates with the host-derived antimicrobial peptides in the innate immune system to reduce survival of an important human bacterial pathogen. |
| first_indexed | 2024-04-13T09:22:28Z |
| format | Article |
| id | doaj.art-bb9143ba02f24f73a030a2a165940046 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T09:22:28Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bb9143ba02f24f73a030a2a1659400462022-12-22T02:52:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0151e855710.1371/journal.pone.0008557Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus.Anna L CogenKenshi YamasakiJun MutoKatheryn M SanchezLaura Crotty AlexanderJackelyn TaniosYuping LaiJudy E KimVictor NizetRichard L GalloAntimicrobial peptides play an important role in host defense against pathogens. Recently, phenol-soluble modulins (PSMs) from Staphylococcus epidermidis (S. epidermidis) were shown to interact with lipid membranes, form complexes, and exert antimicrobial activity. Based on the abundance and innocuity of the cutaneous resident S. epidermidis, we hypothesized that their PSMs contribute to host defense. Here we show that S. epidermidis delta-toxin (PSMgamma) is normally present in the epidermis and sparsely in the dermis of human skin using immunohistochemistry. Synthetic delta-toxin interacted with neutrophil extracellular traps (NETs) and colocalized with cathelicidin while also inducing NET formation in human neutrophils. In antimicrobial assays against Group A Streptococcus (GAS), delta-toxin cooperated with CRAMP, hBD2, and hBD3. In whole blood, addition of delta-toxin exerted a bacteriostatic effect on GAS, and in NETs, delta-toxin increased their killing capacity against this pathogen. Coimmunoprecipitation and tryptophan spectroscopy demonstrated direct binding of delta-toxin to host antimicrobial peptides LL-37, CRAMP, hBD2, and hBD3. Finally, in a mouse wound model, GAS survival was reduced (along with Mip-2 cytokine levels) when the wounds were pretreated with delta-toxin. Thus, these data suggest that S. epidermidis-derived delta-toxin cooperates with the host-derived antimicrobial peptides in the innate immune system to reduce survival of an important human bacterial pathogen.http://europepmc.org/articles/PMC2796718?pdf=render |
| spellingShingle | Anna L Cogen Kenshi Yamasaki Jun Muto Katheryn M Sanchez Laura Crotty Alexander Jackelyn Tanios Yuping Lai Judy E Kim Victor Nizet Richard L Gallo Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus. PLoS ONE |
| title | Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus. |
| title_full | Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus. |
| title_fullStr | Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus. |
| title_full_unstemmed | Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus. |
| title_short | Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus. |
| title_sort | staphylococcus epidermidis antimicrobial delta toxin phenol soluble modulin gamma cooperates with host antimicrobial peptides to kill group a streptococcus |
| url | http://europepmc.org/articles/PMC2796718?pdf=render |
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