Antimicrobial Compound Production By Engineered Bacteria Against Opportunistic Pathogens in Atopic Dermatitis Skin

Atopic dermatitis (AD) is an inflammatory skin condition that is characterized by chronic itching of the skin associated with Staphylococcus aureus overgrowth. Current treatment approaches such as topical steroids, antiseptic washes, and biologics are costly, and have undesirable side effects. In this study, a bacterial host is engineered to produce antimicrobial compounds that are effective against S. aureus. Since AD skin is prone to secondary infections caused by opportunistic pathogenic commensals, we also explored the ability of these antimicrobial compounds to inhibit opportunistic pathogens, including Pseudomonas aeruginosa and Cutibacterium acnes. In the presence of the substrate glycerol, our engineered host enabled the production of reuterin, a potent antimicrobial metabolite in the solution. We observed a significant inhibition in all three opportunistic pathogens in the presence of the engineered bacteria as compared to the wild type. Further optimizations will be carried out to ensure the efficacy and safety of these engineered organisms. Ultimately, the effects of the antimicrobial metabolites on the skin’s microbiome will be investigated—this would uncover whether these metabolites will worsen dysbiosis or restore the abundance of healthy commensals on the skin.