Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 140, Issue 47, Pages 16140-16151Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.8b08711
Keywords
-
Categories
Funding
- National Institutes of Health [R01GM117278, NIH-CA031845]
- Singapore National Medical Research Council [NMRC/CBRG/0086/2015]
- Stanford Center for Molecular Analysis and Design
- National Science Foundation
Ask authors/readers for more resources
New strategies are urgently needed to target MRSA, a major global health problem and the leading cause of mortality from antibiotic-resistant infections in many countries. Here, we report a general approach to this problem exemplified by the design and synthesis of a vancomycin-D-octaarginine conjugate (V-r8) and investigation of its efficacy in addressing antibiotic-insensitive bacterial populations. V-r8 eradicated MRSA biofilm and persister cells in vitro, outperforming vancomycin by orders of magnitude. It also eliminated 97% of biofilm-associated MRSA in a murine wound infection model and displayed no acute dermal toxicity. This new dual-function conjugate displays enhanced cellular accumulation and membrane perturbation as compared to vancomycin. Based on its rapid and potent activity against biofilm and persister cells, V-r8 is a promising agent against clinical MRSA infections.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available