A commensal strain of Staphylococcus epidermidis protects against skin neoplasia

• Published in: Science advances Vol. 4; no. 2; p. eaao4502
• Main Authors: Nakatsuji, Teruaki, Chen, Tiffany H., Butcher, Anna M., Trzoss, Lynnie L., Nam, Sang-Jip, Shirakawa, Karina T., Zhou, Wei, Oh, Julia, Otto, Michael, Fenical, William, Gallo, Richard L.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.02.2018
• Subjects: Adenine - analogs & derivatives; Adenine - chemistry; Adenine - metabolism; Adenine - pharmacology; Animals; Cell Line, Tumor; Cell Proliferation - drug effects; Female; Health and Medicine; Humans; Melanoma, Experimental - pathology; Membrane Proteins - metabolism; Mice; SciAdv r-articles; Skin - drug effects; Skin - microbiology; Skin Neoplasms - microbiology; Skin Neoplasms - pathology; Staphylococcus epidermidis - drug effects; Staphylococcus epidermidis - isolation & purification; Staphylococcus epidermidis - physiology; Ultraviolet Rays
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.aao4502

Bacteria within the skin microbiome of some individuals produce an antimetabolite that inhibits tumor growth. We report the discovery that strains of Staphylococcus epidermidis produce 6- N -hydroxyaminopurine (6-HAP), a molecule that inhibits DNA polymerase activity. In culture, 6-HAP selectively inhibited proliferation of tumor lines but did not inhibit primary keratinocytes. Resistance to 6-HAP was associated with the expression of mitochondrial amidoxime reducing components, enzymes that were not observed in cells sensitive to this compound. Intravenous injection of 6-HAP in mice suppressed the growth of B16F10 melanoma without evidence of systemic toxicity. Colonization of mice with an S. epidermidis strain producing 6-HAP reduced the incidence of ultraviolet-induced tumors compared to mice colonized by a control strain that did not produce 6-HAP. S. epidermidis strains producing 6-HAP were found in the metagenome from multiple healthy human subjects, suggesting that the microbiome of some individuals may confer protection against skin cancer. These findings show a new role for skin commensal bacteria in host defense.