Photosensitization of Bacterial Pathogens through Small Molecule Activators of Heme Biosynthesis
Abstract
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 utilize a unique heme biosynthesis pathway, which implicates this pathway as a novel target for development of antibacterial therapies. We report here the identification of a small molecule activator of coproporphyrinogen oxidase (HemY) from Gram-positive bacteria, an enzyme essential for heme biosynthesis. Activation of HemY induces accumulation of coproporphyrin III and leads to photosensitization of Gram-positive pathogens. In combination with light, HemY activation reduces bacterial burden and tissue ulceration in murine models of SSTI. Thus, small molecule activation of HemY represents an effective strategy for the development of light-bases antimicrobial therapies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2017
- Accession Number
- AD1059208
Entities
People
- Duco Jansen
- Eric P. Skaar
- Gary Sulikowski
Organizations
- Vanderbilt University