Optimization of optical parameters for improved photodynamic therapy of Staphylococcus aureus using endogenous coproporphyrin III.

Background: It has recently been shown that endogenous photosensitization of Gram-positive bacteria is achieved through the accumulation of the heme precursor coproporphyrin III and not protoporphyrin IX, as was previously assumed. As previous studies have operated under this assumption, the efficacy of optimal targeting of the absorption peaks of coproporphyrin III has not been explored.

Methods: Staphylococcus aureus was endogenously photosensitized through the addition of either the small molecule VU0038882, aminolevulinic acid, or both.

Antibacterial photosensitization through activation of coproporphyrinogen oxidase.

Gram-positive bacteria cause 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 biosynthesis pathway, which implicates this pathway as a target for development of antibacterial therapies. We report here the identification of a small-molecule activator of coproporphyrinogen oxidase (CgoX) from Gram-positive bacteria, an enzyme essential for heme biosynthesis.