1. Endolysin Inhibits Skin Colonization by Patient-Derived Staphylococcus Aureus and Malignant T-Cell Activation in Cutaneous T-Cell Lymphoma.
- Author
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Pallesen EMH, Gluud M, Vadivel CK, Buus TB, de Rooij B, Zeng Z, Ahmad S, Willerslev-Olsen A, Röhrig C, Kamstrup MR, Bay L, Lindahl L, Krejsgaard T, Geisler C, Bonefeld CM, Iversen L, Woetmann A, Koralov SB, Bjarnsholt T, Frieling J, Schmelcher M, and Ødum N
- Subjects
- Humans, Staphylococcus aureus, Skin microbiology, Recombinant Proteins, T-Lymphocytes, Staphylococcal Infections microbiology, Lymphoma, T-Cell, Cutaneous drug therapy, Skin Neoplasms drug therapy, Skin Neoplasms microbiology
- Abstract
Staphylococcus aureus is suspected to fuel disease activity in cutaneous T-cell lymphomas. In this study, we investigate the effect of a recombinant, antibacterial protein, endolysin (XZ.700), on S. aureus skin colonization and malignant T-cell activation. We show that endolysin strongly inhibits the proliferation of S. aureus isolated from cutaneous T-cell lymphoma skin and significantly decreases S. aureus bacterial cell counts in a dose-dependent manner. Likewise, ex vivo colonization of both healthy and lesional skin by S. aureus is profoundly inhibited by endolysin. Moreover, endolysin inhibits the patient-derived S. aureus induction of IFNγ and the IFNγ-inducible chemokine CXCL10 in healthy skin. Whereas patient-derived S. aureus stimulates activation and proliferation of malignant T cells in vitro through an indirect mechanism involving nonmalignant T cells, endolysin strongly inhibits the effects of S. aureus on activation (reduced CD25 and signal transducer and activator of transcription 5 phosphorylation) and proliferation (reduced Ki-67) of malignant T cells and cell lines in the presence of nonmalignant T cells. Taken together, we provide evidence that endolysin XZ.700 inhibits skin colonization, chemokine expression, and proliferation of pathogenic S. aureus and blocks their potential tumor-promoting effects on malignant T cells., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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