The discovery of penicillin and the widespread use of antibiotics to control infectious disease has been one of the most important innovations of the 20th century. However during the last decades several available antibiotics became ineffective due to evolutionary changes in bacteria that allow them to survive these powerful drugs. Multi-drug resistance efflux transporters threaten to reverse the progress of treating infectious disease by extruding a wide range of drug and other cytotoxic compounds. These proteins are embedded in the cell membrane and their function is to bind and transport a broad range of substrate out of the cell. Yet high- resolution structures of multi-drug resistant proteins have been solved, however those examples do not provide enough information to describe thoroughly the mechanism of multi-drug resistance.
Also less are known about such a bacteria which are the causing the major problems in nosocomial infections. The major focus of this project is to clone, over-express, functionally characterize, purify, crystallize and solve the structure of MDR transporters of DMT (Drug Metabolite Transporter) and MOP (Mulitdrug/Oligosaccharidyl-lipid/Polysaccharide Flippase) without and/or with their ligands to provide additional insight into the mul tidrug resistance of Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa and Staphylococcus aureus. The structural information will provide a basis for developing new, more effective drugs to treat serious infections.
Fields of science
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