Synergistic antibiotics combinations targeting the bacterial ribosomes. The antibiotics market generated sales of $42 billion in 2009 globally, representing 5% of the global pharmaceutical market. With the increased use of antibiotics to treat bacterial infections, pathogenic strains have acquired antibiotic resistance. The decrease in antibiotics? effectiveness has led to a growing need for novel or improved antibacterial agents. However, single agents directed at an individual target frequently show limited efficacies and poor safety and resistance profiles. Combination therapy with single-target inhibitors is standard therapy against several conditions such as HIV and Helicobacter pylori. The outlined technology employs a structural analysis approach to develop a novel two-component antibiotic with synergistic activity.
• Treatment of a variety of Gram-positive infections
• Improvements of the inhibitory action of the Antibiotics
• Anti-cancer combination therapy
• Synergistic action
• Treatment is less likely to result in the emergence of antibiotic resistance
Prof. Ada Yonath, 2009 Nobel Laureate in Chemistry, and colleagues from Weizmann Institute of Science have discovered the sites of binding and the modes of action of two antibacterial agents, lankamycin (LM) and lankacidin, (LC) by crystallographic and biochemical analyses. These two compounds, produced by Streptomyces rochei, bind at neighboring sites in the large ribosomal subunit, and inhibit successive steps in protein synthesis: formation of the nascent protein chain and its export from the ribosome. Such simultaneous inhibition of bacterial growth results in a synergistic action of these two drugs. Based on these structural studies means for enhancing the synergetic inhibitory effect of LC and LM are also provided. This novel technology demonstrates the utility of structural analysis for providing new directions for drug discovery.