Antibacterial photosensitization through activation of coproporphyrinogen oxidase

Autor: Jocelyn Simpson, Audra R. Fullen, Matthew E. Albertolle, Lisa J. Lojek, Gary A. Sulikowski, Kenneth J. Salleng, E. Duco Jansen, R. Nagarajan, Matthew C. Surdel, Brendan F. Dutter, Pedro L. Teixeira, Harry A. Dailey, Eric P. Skaar, Jeremy B. Ford, J. Logan Jenkins, Dennis J. Horvath, D. Borden Lacy, Ivelin S. Georgiev
Rok vydání: 2017
Předmět:
Zdroj: Proceedings of the National Academy of Sciences. 114
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.1700469114
Popis: Significance Skin and soft tissue infections (SSTIs) account for a majority of visits to hospitals and clinics in the United States and are typically caused by Gram-positive pathogens. Recently, it was discovered that Gram-positive bacteria use a unique pathway to synthesize the critical cellular cofactor heme. The divergence of the heme biosynthesis pathways between humans and Gram-positive bacteria provides a unique opportunity for the development of new antibiotics targeting this pathway. We report here the identification of a small-molecule activator of coproporphyrinogen oxidase (CgoX) from Gram-positive bacteria that 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.
Databáze: OpenAIRE