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SLUSH peptides of the PSMβ family enable Staphylococcus lugdunensis to use erythrocytes as a sole source of nutrient iron

Sekar, Sharmila ; Schwarzbach, Selina ; Nega, Mulugeta ; Bloes, Dominik Alexander ; Smeds, Emanuel LU ; Kretschmer, Dorothee ; Foster, Timothy J. and Heilbronner, Simon (2024) In FASEB Journal 38(16).
Abstract

During infection, the host employs nutritional immunity to restrict access to iron. Staphylococcus lugdunensis has been recognized for its ability to utilize host-derived heme to overcome iron restriction. However, the mechanism behind this process involves the release of hemoglobin from erythrocytes, and the hemolytic factors of S. lugdunensis remain poorly understood. S. lugdunensis encodes four phenol-soluble modulins (PSMs), short peptides with hemolytic activity. The peptides SLUSH A, SLUSH B, and SLUSH C are β-type PSMs, and OrfX is an α-type PSM. Our study shows the SLUSH locus to be essential for the hemolytic phenotype of S. lugdunensis. All four peptides individually exhibited hemolytic activity against human and sheep... (More)

During infection, the host employs nutritional immunity to restrict access to iron. Staphylococcus lugdunensis has been recognized for its ability to utilize host-derived heme to overcome iron restriction. However, the mechanism behind this process involves the release of hemoglobin from erythrocytes, and the hemolytic factors of S. lugdunensis remain poorly understood. S. lugdunensis encodes four phenol-soluble modulins (PSMs), short peptides with hemolytic activity. The peptides SLUSH A, SLUSH B, and SLUSH C are β-type PSMs, and OrfX is an α-type PSM. Our study shows the SLUSH locus to be essential for the hemolytic phenotype of S. lugdunensis. All four peptides individually exhibited hemolytic activity against human and sheep erythrocytes, but synergism with sphingomyelinase was observed exclusively against sheep erythrocytes. Furthermore, our findings demonstrate that SLUSH is crucial for allowing the utilization of erythrocytes as the sole source of nutritional iron and confirm the transcriptional regulation of SLUSH by Agr. Additionally, our study reveals that SLUSH peptides stimulate the human immune system. Our analysis identifies SLUSH as a pivotal hemolytic factor of S. lugdunensis and demonstrates its concerted action with heme acquisition systems to overcome iron limitation in the presence of host erythrocytes.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
erythrocytes, hemolysis, iron acquisition, PSMs, SLUSH
in
FASEB Journal
volume
38
issue
16
article number
e23881
publisher
Wiley
external identifiers
  • pmid:39166718
  • scopus:85201584753
ISSN
0892-6638
DOI
10.1096/fj.202400335R
language
English
LU publication?
yes
id
302a8b1a-adb1-4de2-97a9-859f61b19081
date added to LUP
2024-10-30 12:41:09
date last changed
2025-07-10 11:13:19
@article{302a8b1a-adb1-4de2-97a9-859f61b19081,
  abstract     = {{<p>During infection, the host employs nutritional immunity to restrict access to iron. Staphylococcus lugdunensis has been recognized for its ability to utilize host-derived heme to overcome iron restriction. However, the mechanism behind this process involves the release of hemoglobin from erythrocytes, and the hemolytic factors of S. lugdunensis remain poorly understood. S. lugdunensis encodes four phenol-soluble modulins (PSMs), short peptides with hemolytic activity. The peptides SLUSH A, SLUSH B, and SLUSH C are β-type PSMs, and OrfX is an α-type PSM. Our study shows the SLUSH locus to be essential for the hemolytic phenotype of S. lugdunensis. All four peptides individually exhibited hemolytic activity against human and sheep erythrocytes, but synergism with sphingomyelinase was observed exclusively against sheep erythrocytes. Furthermore, our findings demonstrate that SLUSH is crucial for allowing the utilization of erythrocytes as the sole source of nutritional iron and confirm the transcriptional regulation of SLUSH by Agr. Additionally, our study reveals that SLUSH peptides stimulate the human immune system. Our analysis identifies SLUSH as a pivotal hemolytic factor of S. lugdunensis and demonstrates its concerted action with heme acquisition systems to overcome iron limitation in the presence of host erythrocytes.</p>}},
  author       = {{Sekar, Sharmila and Schwarzbach, Selina and Nega, Mulugeta and Bloes, Dominik Alexander and Smeds, Emanuel and Kretschmer, Dorothee and Foster, Timothy J. and Heilbronner, Simon}},
  issn         = {{0892-6638}},
  keywords     = {{erythrocytes; hemolysis; iron acquisition; PSMs; SLUSH}},
  language     = {{eng}},
  number       = {{16}},
  publisher    = {{Wiley}},
  series       = {{FASEB Journal}},
  title        = {{SLUSH peptides of the PSMβ family enable Staphylococcus lugdunensis to use erythrocytes as a sole source of nutrient iron}},
  url          = {{http://dx.doi.org/10.1096/fj.202400335R}},
  doi          = {{10.1096/fj.202400335R}},
  volume       = {{38}},
  year         = {{2024}},
}