Scientists engineer smart bacteria that live in your skin to treat acne

In a study led by the Translational Synthetic Biology Laboratory Department of Medicine and Life Sciences ( ) at Pompeu Fabra University, an international research team has successfully engineered Cutibacterium acnes, a type of skin bacterium, to secrete a therapeutic molecule to treat acne symptoms.

This innovative approach holds promise for addressing skin alterations and other diseases using living therapeutics. Engineering smart skin bacteria The study reveals that the researchers have edited the genome of Cutibacterium acnes to produce the NGAL protein, a mediator of the acne drug isotretinoin.

This protein has been proven to reduce sebum production by inducing the death of sebocytes, the skin cells responsible for sebum secretion. “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,” says Nastassia Knödlseder, the study's first author. Cutibacterium acnes was traditionally considered an intractable bacterium, posing challenges in introducing DNA and producing proteins. However, the researchers, led by Marc Güell, successfully overcame these obstacles by improving DNA delivery, stability, and gene expression.

The synthetic bacterium developed has safety features to enable real life applications, a crucial step for future human . “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.

Moving beyond acne treatment The engineered bacterium is not limited to acne treatment. Marc Güell envisions a technology platform that can edit any bacteria to treat multiple diseases. The team is exploring the potential of using C. acnes for skin sensing applications and immune modulation applications.

“We have developed a technology platform that opens the door to editing any bacteria to treat multiple diseases. We are now focused on using C. acnes to treat acne, but we can deliver genetic circuits to create smart microbes for applications related to skin sensing or immune modulation,” highlights Marc Güell.

Future prospects: Project ‘SkinDev’ This research initiative will continue under the European Project ‘SkinDev,’ where scientists from the Translational Synthetic Biology lab and its partners will engineer C. acnes to address atopic dermatitis. This chronic cutaneous inflammatory condition characterized by dry skin, eczema, and severe irritation, especially common among young children, presents another avenue for applying .

While the road to human therapeutics requires careful validation, the researchers express optimism, given the prior safe and effective testing of non engineered C. acnes on patients' skin. The potential for this innovative approach to revolutionize the treatment landscape for various skin conditions is on the horizon.

The collaborative effort of scientists from institutions such as the Bellvitge Biomedical Research Institute, the University of Barcelona, and others underscores the significance of this breakthrough in synthetic biology for medical applications. This marks a significant leap towards personalized and targeted skin treatment therapies, showcasing engineered bacteria's potential as living therapeutics.

The study was published in . : Microorganisms can be equipped with synthetic genetic programs for the production of targeted therapeutic molecules. Cutibacterium acnes is the most abundant commensal of the human skin, making it an attractive chassis to create skin delivered therapeutics. Here, we report the engineering of this bacterium to produce and secrete the therapeutic molecule neutrophil gelatinase associated lipocalin, in vivo, for the modulation of cutaneous sebum production..