Skin cancer: the protective effect of some Staphylococcus epidermidis strains

Vignette

An American team has discovered an anti-tumoral molecule produced by certain Staphylococcus epidermidis strains that are commensal bacteria of the cutaneous microbiota. This could lead to new methods for treating and even preventing skin cancers.

 

S. epidermidis is one of the dominant species in the cutaneous microbiota, along with other species of the coagulase-negative Staphylococcus genus. These commensal bacteria fight against pathogenic bacteria, but they also have the capacity to strengthen skin immune defenses by triggering the production of antimicrobial peptides by keratinocytes to destroy pathogens such as Staphylococcus aureus (which often colonizes the skin of atopic skins) or Group A streptococci (GAS).

Targeting cancer cells

In trying to clarify the antimicrobial effect of coagulase-negative Staphylococcus strains, American researchers discovered a new anti-GAS bactericidal molecule in samples of healthy human skin: 6‑HAP (6-N-hydroxyaminopurine), a nitrogenous base with a structure similar to adenine. It is thought to block DNA synthesis by disrupting the A-T (adenine-thymine) pairing.  Other nitrogenous base analogs that have already been used, such as 6-mercaptopurine in the treatment of acute leukemia, have a similar action. In this study, 6-HAP proved to be active in murine melanoma and lymphoma cell cultures, without being harmful to  non-cancerous keratinocyte cultures (NHEK). This protection by 6-HAP of healthy cells against cytotoxicity is thought to be explained in part by the action of certain mitochondrial reductive enzymes operating in cell detoxification processes.

A significant anti-tumoral effect

After having verified that 6-HAP does not exert a mutagenic effect in vitro, and that it does not exhibit perceptible systemic toxicity in mice, the team tested its anti-tumoral efficacy in murine fast-growing melanoma models. This was met with success: tumor size was reduced by more than 60% compared to control mice. In mice predisposed to UV-induced skin cancer, topical application of S. epidermidis (at a bacterial density mimicking that found in the colonization of healthy human skin) even allowed a significant reduction in the incidence and number of tumors (squamous papilloma) compared to the effect observed in mice colonized by a non-6-HAP-producing strain of  S. epidermidis. Other experiments should confirm the protective effect of 6-HAP-producing strains of S. epidermidis against different skin cancers and their possible benefit in primary prevention. The researchers believe that these results represent the first description of the protective effect of a commensal bacterium of the skin against abnormal cell proliferation, similarly to intestinal bacteria that produce short-chain fatty acids. They also add that the harmful effect of the dysbiosis might be due to the loss of the protective function of the microbiota rather than to the acquisition of an impaired bacterial community.

 

Sources:

Nakatsuji T et al. A commensal strain of Staphylococcus epidermidis protects against skin neoplasia.Sci Adv. 2018 Feb; 4(2): eaao4502.