Antibacterial photosensitization through activation of coproporphyrinogen oxidase
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 24, 2017
- Source ID
- 10.1073/pnas.1700469114
Entities
People
- Audra R. Fullen
- Brendan F. Dutter
- D. Borden Lacy
- Dennis J. Horvath Jr.
- E Duco Jansen
- Eric P. Skaar
- Gary A. Sulikowski
- Harry A. Dailey
- Ivelin S. Georgiev
- J. Logan Jenkins
- Jeremy B Ford
- Jocelyn Simpson
- Kenneth J. Salleng
- Lisa J. Lojek
- Matthew Albertolle
- Matthew C. Surdel
- Pedro L. Teixeira
- Raju Nagarajan
Organizations
- National Institutes of Health
- University of Georgia
- Vanderbilt University
- Walter Reed Army Institute of Research