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

Journal of Investigative Dermatology
Open Access

Clinical Summary

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What was studied

Preclinical in vitro and ex vivo experiments tested a recombinant anti–Staphylococcus aureus endolysin (XZ.700) on patient-derived S. aureus growth, skin colonization (healthy and lesional CTCL skin), and S. aureus–driven malignant T‑cell activation/proliferation.

Key findings

XZ.700 cut S. aureus counts by ≥4-log CFU at ≥1 mg/mL within 1 hour and dropped SEA toxin from >15 ng/mL to <1 ng/mL at 4 hours; on skin, 1 µg/mL coaddition nearly prevented colonization and 10 µg/mL after colonization almost eradicated bacteria, while also suppressing S. aureus–induced IFNγ/CXCL10 and blocking CD25/pSTAT5 and Ki‑67 increases in malignant T cells in coculture.

Study limitations

Findings are limited to laboratory and ex vivo models with small human tissue samples (five lesional sites from three patients), using few bacterial isolates; several authors are affiliated with the endolysin’s developer.

Clinical implications

In CTCL models, targeted S. aureus killing with an endolysin curtailed skin colonization and halted S. aureus–driven malignant T‑cell activation, suggesting a potential nonantibiotic decolonization strategy that warrants clinical testing.