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T Nakatsuji, TH Chen, AM Butcher, LL Trzoss, SJ Nam, KT Shirakawa, W Zhou, J Oh, M Otto, W Fenical and RL Gallo
Abstract
We report the discovery that strains ofStaphylococcus epidermidisproduce 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 anS. epidermidisstrain 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. epidermidisstrains 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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Concepts
Adenosine triphosphate, Neoplasm, Tumor, Bacteria, Enzyme, DNA polymerase I, Cancer, DNA
MeSH headings
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