A commensal strain of Staphylococcus epidermidis protects against skin neoplasia

Teruaki Nakatsuji, Tiffany H. Chen, Anna M. Butcher, Lynnie L. Trzoss, Sang Jip Nam, Karina T. Shirakawa, Wei Zhou, Julia Oh, Michael Otto, William Fenical, Richard L. Gallo

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

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 associatedwith the expression of mitochondrial amidoxime reducing components, enzymes that were not observed in cells sensitive to this compound. Intravenous injection of 6-HAP inmice suppressed the growth of B16F10 melanomawithout 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 individualsmay confer protection against skin cancer. These findings show a new role for skin commensal bacteria in host defense.

Original languageEnglish
Article numbereaao4502
JournalScience Advances
Volume4
Issue number2
DOIs
StatePublished - 28 Feb 2018

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