2019-002 – Copper-activated Drugs Against Gram-positive Multidrug-resistant Bacteria (e.g. MRSA)

Antibiotic resistance has become a worldwide health concern. A steadily increasing number of resistant bacteria endanger the efficacy of antibiotic drugs that are available on the market and lead to the critical need for developing new drug candidates. However, only a few innovative approaches to developing new antibiotics are discernible. 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 (I) 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 (I) – drug complexes have to kill bacteria very effectively. Kansas State University researchers in collaboration with researchers at University of Alabama Birmingham Medical Center have discovered novel compounds that are highly effective against Methicillin-resistant Staphylococcus aureus (MRSA) and other gram-positive strains. These compounds show micromolar to nanomolar half maximal inhibitory concentrations (IC50) in the presence of copper (I), whereas they show low or virtually no toxicity in its absence. Caronda Moore caronda@ksu.edu 785-532-1366

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