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Sci Adv. 2018 Feb 28;4(2):eaao4502. doi: 10.1126/sciadv.aao4502. eCollection 2018 Feb.

A commensal strain of Staphylococcus epidermidis protects against skin neoplasia.

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Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA.
Scripps Institute of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA.
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.


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.

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