Researchers at Pompeu Fabra University have developed a genetic toolkit that can be used to engineer Cutibacterium acnes, the most common bacteria found on human skin, to produce therapeutic compounds for various skin conditions. This approach offers a safe, controlled, and advantageous alternative to existing treatments.
The study, published in the scientific journal Cell Systems, was led by Dr. Marc Güell, with Guillermo Nevot as co-first author. The researchers successfully engineered a strain of C. acnes that produces antioxidants and reduces oxidative stress in skin cells exposed to UV radiation. While the research is currently in the cell culture stage, it holds great promise for future applications.
The genetic toolkit consists of a circular DNA molecule called a plasmid, which includes different sequences, each with a specific function. One sequence encodes the gene for producing the desired therapeutic compound, another regulates the amount of compound produced based on external stimuli, another allows for selection of strains that have integrated the plasmid, and another removes antibiotic resistance after the selection process.
The researchers also introduced tools to eliminate C. acnes's natural ability to produce certain nutrients it needs. This ensures that the bacteria will not persist on the skin unless those nutrients are provided externally, for example, through a cream applied to the skin.
The genetic toolkit makes these bacteria safe because they do not contain antibiotic resistance genes, cannot exchange them with other bacteria, and cannot produce the nutrients they need to survive on their own.
Oxidative stress, caused by factors like UV radiation and chronic inflammation, damages cells and alters their structure and function. The researchers engineered a strain of C. acnes to produce more or less antioxidants in response to different levels of artificial stimuli in the laboratory. When applied to a culture of keratinocytes, the most superficial cells of the skin, exposed to UV radiation, the antioxidants generated by C. acnes significantly reduced oxidative stress. This reduction correlated with the activity levels of the engineered gene, suggesting that the antioxidant activity of the bacteria can be adjusted to specific needs.
In the future, cosmetic and therapeutic creams could be formulated with millions of C. acnes capable of producing varying levels of antioxidants in response to natural stimuli like oxidative stress levels in the skin. This could lead to treatments for conditions such as atopic dermatitis, premature aging, and cancer.
C. acnes resides in hair follicles, where it metabolizes sebum, the oily substance produced by the skin. It forms stable and long-lasting populations with genetically similar individuals, with minimal interaction with other bacterial species and limited gene transfer.
Strains II and III of C. acnes are associated with healthy skin. In fact, certain skin diseases, such as atopic dermatitis, exhibit a characteristic decrease in C. acnes on the skin. Additionally, C. acnes can be easily transplanted from a healthy donor to a recipient through topical applications to improve skin health.
Other genetically engineered bacterial species have shown promising results in treating metabolic diseases, infections, and cancer in the gut and lungs. However, there are few studies on skin conditions. The most promising studies, conducted on mice, involved Staphylococcus epidermidis to accelerate wound healing, as vaccines against cancer, and as mosquito repellents. However, S. epidermidis does not naturally reside on our skin, its integration is low, populations change more frequently, and it is more prone to exchanging genes with other bacteria.
Therefore, the characteristics of C. acnes, combined with the genetic toolkit, make it a safe and ideal candidate for therapeutic use, filling a niche that has been under-researched.