Reprogramming a common cutaneous bacterium to increase skin hydration
Grantee: Nastassia Knödlseder, Postdoc, Pompeu Fabra University
Amount: DKK 1,985,000
Grant category: LEO Foundation Visiting Researchers
Year: 2025
Geography: Spain
Hyaluronic acid (HA) is a naturally abundant molecule in the human body, with approximately half of its total amount found in the skin, where it plays a critical role in maintaining hydration and viscoelasticity. Cutibacterium acnes, a common skin bacterium predominantly found on the upper body, is generally beneficial to the skin. However, certain strains of C. acnes are capable of inducing inflammation and are linked to acne vulgaris. These strains exhibit HA-degrading activity via the enzyme hylA, which leads to the production of proinflammatory HA fragments.
The proposal hypothesizes that reprogramming C. acnes from a HA-degrading bacterium to a HA-synthesizing one could not only reduce its virulence but also enhance its skin-beneficial functions. To test this, the applicant and the collaborators at AU will create a hylA knock-out strain of C. acnes, replacing the hylA gene with a highly active HA synthase, that has been successfully utilized as a recombinant enzyme for HA synthesis in mice.
The repurposed C. acnes strain will be evaluated in vitro for its (anti-)inflammatory effects on skin cells and in vivo on mouse skin for its engraftment potential and its impact on skin barrier function.
The outcomes of this project may form the basis for exploring the potential of engineered probiotic strains with enhanced host-beneficial properties, ultimately contributing to improved health span.