Membrane Active Vancomycin
Analogues: A Strategy to
Combat Bacterial Resistance
- Publication date
- Publisher
Abstract
The
alarming growth of antibiotic resistant superbugs such as vancomycin-resistant
Enterococci and Staphylococci has become a major global health hazard.
To address this issue, we report the development of lipophilic cationic
vancomycin analogues possessing excellent antibacterial activity against
several drug-resistant strains. Compared to vancomycin, efficacy greater
than 1000-fold was demonstrated against vancomycin-resistant Enterococci
(VRE). Significantly, unlike vancomycin, these compounds were shown
to be bactericidal at low concentrations and did not induce bacterial
resistance. An optimized compound in the series, compared to vancomycin,
showed higher activity in methicillin-resistant Staphylococcus
aureus (MRSA) infected mouse model and exhibited superior
antibacterial activity in whole blood with no observed toxicity. The
remarkable activity of these compounds is attributed to the incorporation
of a new membrane disruption mechanism into vancomycin and opens up
a great opportunity for the development of novel antibiotics