Copper-activated drugs against gram-positive multidrug-resistant bacteria
Kansas State University researchers, in collaboration with researchers at University of Alabama-Birmingham Medical Center, have discovered novel compounds that are highly effective against MRSA, Methicillin-resistant Staphylococcus aureus, and other gram-positive strains. These compounds show micromolar to nanomolar half maximal inhibitory concentrations in the presence of copper, whereas they show low or virtually no toxicity in its absence.
In order to suppress drug resistance, a truly effective strategy has to be synergetic with the host’s response to detecting pathogens. Metal-mediated innate immunity is an important component of the cells’ anti-bacterial machinery. Studies have shown that in bacteria- infected cells, iron and other nutrients are withheld from the phagosomes, in which the bacteria are taken up, while copper is flooded into the phagosomes to induce toxicity. A typical bacterial response is the development of copper-efflux pumps, which can be found in gram-positive and gram-negative bacteria alike. In order to overcome the efficacy of the bacterial efflux pumps, the copper drug complexes have to kill bacteria very effectively.