Antibacterial photosensitization through activation of coproporphyrinogen oxidase. Proc Natl Acad Sci U S A 2017 Aug 08;114(32):E6652-E6659
Date
07/26/2017Pubmed ID
28739897Pubmed Central ID
PMC5559000DOI
10.1073/pnas.1700469114Scopus ID
2-s2.0-85026874355 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
Author List
Surdel MC, Horvath DJ Jr, Lojek LJ, Fullen AR, Simpson J, Dutter BF, Salleng KJ, Ford JB, Jenkins JL, Nagarajan R, Teixeira PL, Albertolle M, Georgiev IS, Jansen ED, Sulikowski GA, Lacy DB, Dailey HA, Skaar EPAuthor
Matthew C. Surdel PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBacterial Proteins
Coproporphyrinogen Oxidase
Coproporphyrins
Disease Models, Animal
Mice
Photosensitizing Agents
Phototherapy
Staphylococcal Skin Infections
Staphylococcus aureus
