Staphylococcus epidermidis Antimicrobial δ-Toxin (Phenol-Soluble Modulin-γ) Cooperates with Host Antimicrobial Peptides to Kill Group A Streptococcus
Open accessAbstract
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.
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Commensal organisms such as strains of Staphylococcus epidermidis found in the skin secrete antibacterial compounds such as phenol-soluble modulins and interact with the host to induce AMP expression or reduce inflammation.
“Commensal organisms such as strains of Staphylococcus epidermidis found in the skin secrete compounds that are themselves antibacterial, such as phenol-soluble modulins,4,5 and also interact with the host to induce AMP expression6 or reduce inflammation.6”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [5]
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- Authors
- Cogen, A. L., Yamasaki, K., Muto, J., Sanchez, K. M., Crotty Alexander, L., Tanios, J., Lai, Y., Kim, J. E., Nizet, V., & Gallo, R. L.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Gallo, Richard L.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-01-05
- Volume
- 5
- Issue
- 1
- Pages
- e8557
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2796718
- OpenAlex
- W2109623513
- Cited by
- 245
- References
- 27
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 17 · 2023: 17 · 2022: 24 · 2021: 19 · 2020: 15 · 2019: 18 · 2018: 12 · 2017: 12 · 2016: 16 · 2015: 9 · 2014: 10 · 2013: 21 · 2012: 15
- FWCI
- 12.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL057345)
- National Institute of Allergy and Infectious Diseases (R56AI083358, R01AI083358)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR45676, R21AR067547, R01AR045676)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
- Keywords
- Staphylococcus epidermidis, delta-toxin, antimicrobial peptides, Streptococcus pyogenes, neutrophil extracellular traps, cathelicidin, LL-37, human beta-defensins, innate immunity, skin microbiome, wound infection, CXCL2, host-pathogen interaction
- MeSH terms
- Animals, Anti-Infective Agents, Bacterial Toxins, Humans, Immunohistochemistry, Mice, Inbred C57BL, Neutrophils, Peptides, Protein Binding, Skin, Spectrum Analysis, Staphylococcus epidermidis, Streptococcus pyogenes, Immunoprecipitation, Mice
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