Antibacterial photosensitization through activation of coproporphyrinogen oxidase

Gram-positive bacteriacause the majority of skin and soft tissue infections (SSTIs), resulting in the most common reason for clinic visits in the United States. Recently, it was discovered that Gram-positive pathogens use a unique heme biosynthesispathway, which implicates this pathway as a target for development of antibacterial therapies. We report here the identification of a small-moleculeactivator of coproporphyrinogenoxidase (CgoX) from Gram-positive bacteria, an enzyme essential for heme biosynthesis. Activation of CgoX induces accumulation of coproporphyrin III and leads to photosensitization of Gram-positive pathogens. In combination with light, CgoX activation reduces bacterial burden in murine models of SSTI. Thus, small-moleculeactivation of CgoX represents an effective strategy for the development of light-based antimicrobial therapies.