2024-05-10| R&DSpecial

Biotech in Beauty: Engineered Skin Bacteria Designed To Treat Acne

by Bernice Lottering
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A new skin bacteria producing a therapeutic molecule that can treat acne has been successfully engineered by a team of researchers. The specifically designed dermatic bacteria have been validated in lab and mouse models, with promising results suggesting that this innovation could revolutionize skin condition treatments and other diseases using living therapeutics.

Innovating Smart Skin Bacteria: A Breakthrough in Acne Treatment and Beyond

An international research team, led by the Translational Synthetic Biology Laboratory at Pompeu Fabra University’s Department of Medicine and Life Sciences (MELIS), has successfully engineered Cutibacterium acnes (C. acnes), a skin bacterium, to efficiently produce and release a therapeutic molecule for treating acne symptoms. Specifically, they edited the genome of C. acnes to generate the neutrophil gelatinase-associated lipocalin (NGAL) protein. NGAL is a protein that is involved in the mechanism of action of the powerful acne drug isotretinoin, also known as 13-cis-retinoic acid and sold under the brand name Accutane among others. It works by mediating sebocyte apoptosis and sebum production. Specifically, NGAL contributes to the reduction of sebum production by triggering the apoptosis (cell death) of sebocytes (the cells responsible for producing sebum), thereby aiding in the treatment of acne.

The study’s first author, Nastassia Knödlseder, says “We have developed a topical therapy with a targeted approach, using what nature already has. We engineered a bacterium that lives in the skin and makes it produce what our skin needs. Here, we focused on treating acne, but this platform can be extended to several other indications.”

Validation of the engineered bacterium was conducted in skin cell lines, with its delivery confirmed in mice. The findings of the study, as published in Nature Biotechnology, showcase the potential of biotech in daily life, and this discovery presents a significant advancement in the potential for engineering previously non-responsive bacteria to tackle skin conditions and other diseases through living therapeutics.

Innovating Acne Treatment Through Synthetic Biology

Acne, a widespread skin condition, arises from pilosebaceous follicle obstruction or inflammation, presenting as whiteheads, blackheads, pustules, or nodules primarily on the face, forehead, chest, upper back, and shoulders, affecting individuals of all ages due to hormonal imbalances, medication, stress, and poor dietary habits. For severe cases, antibiotics are prescribed to target bacteria within the follicles, or isotretinoin, a derivative of vitamin A, is employed to induce apoptosis in sebocytes through NGAL. However, these treatments may cause significant side effects, such as disrupting the homeostasis of skin microbiota due to non-selective bactericidal action or causing photosensitivity in the case of antibiotics, or birth defects and severe skin scaling with isotretinoin. Hence, developing a treatment with fewer adverse effects would be advantageous for individuals grappling with this condition.

Although successful, the engineering of an alternative therapy for acne treatment was not without its challenges. Led by Marc Güell, the team of researchers that engineered C. acnes, mention that the bacterium has a history of being difficult to manipulate genetically. ‘Until now, C. acnes was considered an intractable bacterium. It was incredibly difficult to introduce DNA and get proteins produced or secreted from an element inserted into its genome,’ explains Knödlseder, who is now currently undertaking her postdoc in the UPF Translational Synthetic Biology Laboratory.

The appeal of C. acnes lies in its great potential as a candidate for synthetic biology-based treatments of skin diseases. Its natural habitat deep within hair follicles, where sebum is produced, makes it an ideal target for addressing skin conditions. Additionally, its role in maintaining skin balance and its proximity to key therapeutic targets further enhance its appeal. Furthermore, the successful integration of C. acnes onto human skin in previous studies underscores its potential as a delivery vehicle for therapeutic interventions.

As a result, the team was motivated to overcome the challenges associated with editing the genome of this bacterium, focusing on enhancing DNA delivery, stability, and gene expression in order to successfully edit the genome of this traditionally non-engineerable bacterium. Their approach included implementing regulatory measures to address concerns such as genetic elements and antibiotic resistance. The resulting synthetic bacterium incorporates safety features suitable for real-world applications, laying the groundwork for future human therapeutics.

Diversifying the Therapeutic Research Scope

Marc Güell discussed the development of a technology platform capable of editing various bacteria to target multiple diseases. He mentions that initially, the focus was on utilizing C. acnes to treat acne. However, the potential extends beyond acne treatment; genetic circuits can be delivered to create “smart” microbes for applications such as skin sensing and immune modulation.

Under the European Project ‘SkinDev‘, led by Marc Güell and his team at the Translational Synthetic Biology lab, the research will continue. Their aim is to engineer C. acnes to address atopic dermatitis, a chronic inflammatory skin condition characterized by symptoms like dry skin, eczema, and severe irritation, particularly common among young children. While each therapeutic approach must undergo individual validation, the researchers express optimism about applying these engineered microbes to humans. They note that non-engineered C. acnes has already been safely and effectively tested on patients’ skin.

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