The microbes make a compound that disrupts DNA formation in tumor cells
R. Gallo and Teruaki Nakatsuji/UC San Diego
Certain skin-dwelling microbes may be anticancer superheroes, reining in uncontrolled cell growth. This surprise discovery could one day lead to drugs that treat or maybe even prevent skin cancer.
The bacteria’s secret weapon is a chemical compound that stops DNA formation in its tracks. Mice slathered with one strain of Staphylococcus epidermidis that makes the compound developed fewer tumors after exposure to damaging ultraviolet radiation compared with those treated with a strain lacking the compound, researchers report online February 28 in Science Advances.
The findings highlight “the potential of the microbiome to influence human disease,” says Lindsay Kalan, a biochemist at the University of Wisconsin–Madison.
Staphylococcal species are the most numerous of the many bacteria that normally live on human skin. Richard Gallo and his colleagues were investigating the antimicrobial powers of these bacteria when the team discovered a strain of S. epidermidis that made a compound — 6-N-hydroxyaminopurine, or 6-HAP for short — that looked a lot like one of the building blocks of DNA. “Because of that structure, we wondered if it interfered with DNA synthesis,” says Gallo, a physician scientist at the University of California, San Diego. In a test tube experiment, 6-HAP blocked the enzyme that builds DNA chains and prevented the chains from growing.
Mice treated with a strain of S. epidermidis that does not make the compound 6-HAP and then exposed to ultraviolet rays developed UV-induced tumors (left). The skin of mice who got a strain with the compound remained largely normal (right).
Cancer cells have runaway growth, so the researchers thought the compound might inhibit those cells. Sure enough, 6-HAP stopped DNA formation in different tumor cells grown in the lab. But the compound was not able to do so in normal skin cells. Certain enzymes in normal skin cells deactivated 6-HAP, the researchers found, and the tumor cells tested appeared to lack those enzymes.
Gallo and colleagues found that the compound had an effect both when injected and when applied topically. Among mice injected with skin cancer cells, some received a shot of 6-HAP while others got a dummy shot. Tumors grew in all the mice, but the tumors in mice given the compound were about half the size of those in mice without the compound.
The researchers then spread S. epidermidis on the backs of hairless mice subjected to UV rays. Some mice got a strain that makes 6-HAP; others got a strain that does not. After 12 weeks of being exposed periodically to UV rays, the first group of mice developed only one tumor each, while mice in the second group were saddled with four to six tumors.
S. epidermidis strains might have gained the ability to stop DNA synthesis to prevent other bacteria from growing, Gallo says. In that way, the bacteria protect their homestead from other invading pathogens. “Perhaps we evolved to provide a safe haven for these organisms because they also benefit us when they’re doing this.” The researchers did a small study of existing genetic data from the human skin microbiome and estimate that 20 percent of the human population have S. epidermidis strains that make 6-HAP on their skin, Gallo says.
More work needs to be done to understand how S. epidermidis makes 6-HAP and how much of the compound is on the skin, Kalan says. “It is important to understand how the microbiome interacts with its human host before we can begin to manipulate it for disease treatment.” One approach could be to develop probiotics for the skin — adding helpful bacteria to ward off infection or maybe even prevent cancer, she says.
Along with skin cancer cells, 6-HAP was also able to block DNA synthesis in lymphoma cells, cancerous immune system cells. It’s too early to say, but there is potential for this secret weapon to slay more than one villain.
T. Nakatsuji et al. A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Science Advances. Published online February 28, 2018.
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