Endolysin Inhibits Skin Colonization by Patient-Derived Staphylococcus Aureus and Malignant T-Cell Activation in Cutaneous T-Cell Lymphoma

Staphylococcus aureus (S. aureus) is suspected to fuel disease activity in cutaneous T cell lymphomas (CTCL). Here we investigate the effect of a recombinant, anti-bacterial protein, endolysin, XZ.700, on S. aureus skin colonization and malignant T cell activation. We show that endolysin strongly inhibits proliferation of S. aureus isolated from CTCL 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 Interferon-gamma (IFNγ) and 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 non-malignant T cells, endolysin strongly inhibits the effects of S. aureus on activation (reduced CD25 and STAT5 phosphorylation) and proliferation (reduced Ki67) of malignant T cells and cell lines in the presence of non-malignant 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.