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 |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Coproporphyrins Staphylococcus aureus medicine.drug_class Antibiotics Microbiology Mice 03 medical and health sciences Coproporphyrinogen Oxidase chemistry.chemical_compound Bacterial Proteins medicine Animals Heme chemistry.chemical_classification Photosensitizing Agents Multidisciplinary biology Activator (genetics) Heme biosynthesis Phototherapy biology.organism_classification Antimicrobial Disease Models Animal 030104 developmental biology Enzyme PNAS Plus chemistry Biochemistry Staphylococcal Skin Infections Bacteria |
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 |
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