Journal
ACS CHEMICAL BIOLOGY
Volume 9, Issue 1, Pages 122-127Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cb400490k
Keywords
-
Categories
Funding
- DOD DMRDP program [W81XWH-11-2-0115]
- Army Research Laboratory
- U.S. Army Research Office [W911NF-11-1-0274]
- Military Infectious Diseases Research Program (MIDRP)
- Defense Medical Research and Development Program (DMRDP)
Ask authors/readers for more resources
Infections caused by multi-drug resistant bacteria, particularly Gram-negative bacteria, are an ever-increasing problem. While the development of new antibiotics remains one option in the fight against bacteria that have become resistant to currently available antibiotics, an attractive alternative is the development of adjuvant therapeutics that restore the efficacy of existing antibiotics. We report a small molecule adjuvant that suppresses colistin resistance in multidrug resistant Acinetobacter baumannii and Klebsiella pneumoniae by interfering with the expression of a two-component system. The compound downregulates the pmrCAB operon and reverses phosphoethanolamine modification of lipid A responsible for colistin resistance. Furthermore, colistin-susceptible and colistin-resistant bacteria do not evolve resistance to combination treatment. This represents the first definitive example of a compound that breaks antibiotic resistance by directly modulating two-component system activity.
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