A commensal strain of Staphylococcus epidermidis protects against skin neoplasia.

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 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.

• Authors: 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
• Journal: Science advances (Sci Adv) Vol. 4 Issue 2 Pg. eaao4502 (02 2018) ISSN: 2375-2548 [Electronic] United States
• PMID: 29507878 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Membrane Proteins
• 6-N-hydroxylaminopurine
• Adenine

Topics

• Adenine (analogs & derivatives, chemistry, metabolism, pharmacology)
• Animals
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Female
• Humans
• Melanoma, Experimental (pathology)
• Membrane Proteins (metabolism)
• Mice
• Skin (drug effects, microbiology)
• Skin Neoplasms (microbiology, pathology)
• Staphylococcus epidermidis (drug effects, isolation & purification, physiology)
• Ultraviolet Rays