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Title: Antibacterial photosensitization through activation of coproporphyrinogen oxidase.

Authors: Surdel, Matthew C; Horvath Jr, Dennis J; Lojek, Lisa J; Fullen, Audra R; Simpson, Jocelyn; Dutter, Brendan F; Salleng, Kenneth J; Ford, Jeremy B; Jenkins, J Logan; Nagarajan, Raju; Teixeira, Pedro L; Albertolle, Matthew; Georgiev, Ivelin S; Jansen, E Duco; Sulikowski, Gary A; Lacy, D Borden; Dailey, Harry A; Skaar, Eric P

Published In Proc Natl Acad Sci U S A, (2017 Aug 08)

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 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. 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-molecule activation of CgoX represents an effective strategy for the development of light-based antimicrobial therapies.

PubMed ID: 28739897 Exiting the NIEHS site

MeSH Terms: Animals; Bacterial Proteins/genetics; Bacterial Proteins/metabolism*; Coproporphyrinogen Oxidase/genetics; Coproporphyrinogen Oxidase/metabolism*; Coproporphyrins/biosynthesis*; Coproporphyrins/genetics; Disease Models, Animal; Mice; Photosensitizing Agents/metabolism*; Phototherapy*; Staphylococcal Skin Infections/enzymology*; Staphylococcal Skin Infections/therapy*; Staphylococcus aureus/genetics; Staphylococcus aureus/metabolism*

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