Targeting Multi-Drug Resistant Pathogens with Novel, Low-Toxicity, Broad-Spectrum Conjugated Oligoelectrolyte Antibiotics
Conjugated oligoelectrolytes (COEs). a, COEs share a modular structure that spontaneously integrates into the bacterial membrane. b, COE structural modules. c, COE2-2hexyl structure. d, Comparison of COE structures: COE2-2hexyl, COE2-3C, distyrylbenzene oligoelectrolyte, DSBN.
The emergence of multidrug-resistant (MDR) pathogens threatens a return to the pre-antibiotic era wherein common infections and minor injuries were very often lethal. We have recently discovered and developed a novel class of synthetic compounds —COEs—which are highly efficacious against diverse MDR pathogens, including infections that are virtually untreatable with current antimicrobials. COEs have no structural relationship to any known antibiotic, and bacterial resistance to COEs ranks among the lowest level of any compound tested. We will significantly expand upon our preliminary studies to 1) determine the mechanism(s) by which COEs act as powerful antimicrobials and by which bacterial pathogens attain resistance; and 2) determine whether COEs can serve as molecular adjuvants to improve the antimicrobial activity of conventional antibiotics. The long-range vision of this multi-disciplinary effort is to establish a new standard for drug design and treatments for MDR pathogens.
