A strain of Staphylococcus epidermidis, a common microbe on healthy human skin, produces a chemical compound that has the ability to impair growth of skin neoplasia, researchers have found. The compound, 6-N-hydroxyaminopurine (6-HAP), inhibits DNA synthesis and exerts selective antiproliferative activity against tumor cell lines, in addition to the ability to suppress ultraviolet (UV)-induced tumor growth.
“These observations suggest that the skin microbiome may contribute to aspects of host defense that include resistance to tumor growth,” the investigators, led by Teruaki Nakatsuji at the University of California, San Diego, La Jolla, wrote in Science Advances.
As part of their experiments, they administered 6-HAP intravenously or applied it topically to mice and then conducted molecular analyses of the effects. They found that
6-HAP directly inhibited DNA synthesis by interfering with adenosine-thymidine base pairing, but did not affect nontransformed human keratinocytes, which suggests that 6-HAP has selective antiproliferative activity.
The investigators also discovered that 6-HAP, when administered intravenously to mice, had no systemic toxic effects and selectively suppressed a rapidly growing melanoma cell line by more than 60% compared with injection of the vehicle alone. In addition, S. epidermidis strains producing 6-HAP on the skin surface offered protection against tumor formation when mice were exposed to UV radiation.
Using whole-genome sequencing, the authors established that 6-HAP production by S. epidermidis was not rare “but universal among all S. epidermidis strains.”
The researchers concluded that commensal skin bacteria may assist in defending the host against skin neoplasia. “Further study is needed to examine whether a loss of S. epidermidis strains producing 6-HAP increases a risk of skin cancer in humans or could be used as a preventative treatment,” they wrote.
Teruaki Nakatsuji, Tiffany H. Chen, Anna M. Butcher, et al. "A commensal strain of Staphylococcus epidermidis protects against skin neoplasia," Science Advances. Feb. 28, 2018. DOI:10.1126/sciadv.aao4502