Partners in defense against skin cancer

What is the skin microbiome?

The trillions of bacteria, fungi and viruses that live on the skin all over our bodies is part of the microbiome. JAX Associate Professor Julia Oh studies the human microbiome for its potential to deliver treatments for infectious and other diseases.

Since their discovery long ago as agents of disease and infection, bacteria and other microbes — “germs,” as it were — have been regarded as our adversaries. Cleanliness to the point of sterility is indeed desirable in certain situations, such as operating rooms, but in normal settings our relationship with microbes is far more complex. As research progresses and we learn more about our microbiomes, the collection of microbes we host, we also learn more about how they can play very  When good bacteria go bad… our bodies can turn against us.It is a new frontier in human health: Revealing the powers of our own microbes to fundamentally change our understanding of diseases of all kinds. important roles in our health and well-being .

A new aspect of this kind of positive effect was recently discovered in a commensal (beneficial) bacteria strain known as Staphylococcus epidermidis. Some staphylococcal species, such as Staphylococcus aureus, are known to contribute to skin disease, but others, including S. epidermidis, are commonly found in healthy skin microbial ecosystems. Indeed, S. epidermidis has been shown to selectively kill pathogens, including S. aureus, as well as improve skin immune function and diminish inflammation. Now, a recent paper published in Science Advances presents evidence of an even more dramatic benefit: protection against skin cancer.

A research group led by Richard Gallo, Ph.D., from the University of California, San Diego, and including JAX Assistant Professor Julia Oh, Ph.D.Our central goal is to develop microbiome therapeutics to treat human disease. We use diverse tools like genomics and synthetic biology to investigate our microbiome’s role in our health and engineer therapeutics.Julia Oh, Ph.D. , discovered that certain strains of S. epidermidis produce a molecule that suppresses tumor growth. The structure of the molecule, 6-N-hydroxyaminopurine (6-HAP), is similar to the DNA base adenine, to the point that it interferes with DNA synthesis. In quickly dividing cells that require rapid DNA replication, such as tumor cells, this can effectively shut down growth.

Working with mice, they found that a S. epidermidis strain that produces 6-HAP significantly decreased cancer initiation compared to a different strain with no 6-HAP production. Also, 6-HAP on its own suppressed the growth of aggressive melanoma when delivered intravenously. Interestingly, the researchers saw no adverse side effects of 6-HAP activity, even though normal skin cells that also divide quickly could be in line for damage as well. Investigating further, they found much higher levels of enzymes that neutralize the activity of 6-HAP in skin cells than in cancer cells, making its activity selective for the tumor cells.

Alterations in the microbiome have been previously implicated in promoting cancer. The findings in the paper suggest that a healthy skin microbiome may provide protection from tumor growth, which is lost when the ecosystem is disrupted. They also provide an intriguing area for study to examine whether S. epidermidis strains that produce 6-HAP may be employed as a preventative skin cancer treatment.

Nakatsuji T et al. 2018. A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Sci Adv 4 (2). DOI: 10.1126/sciadv.aao4502