Disciplines

Medicine and Health Sciences

Abstract

The growing problem of antibiotic resistance is a pressing issue in the world today. By understanding mechanisms of resistance and the compounds involved, enzymes responsible for these resistance processes can be targeted with inhibitory compounds with the end result of restored antibiotic sensitivity. The enzyme BshA is used by many Gram negative bacteria as the committed step of bacillithiol synthesis as a method of antibacterial resistance to fosfomycin. A total structural and mechanistic understanding of BshA is necessary for the design and search for inhibitors for this enzyme. Using knowledge gained in the Cook lab over the past year through X-ray crystallographic structures of BshA with various ligands, a free molecular docking program has been used to start the process of identifying potential inhibitors for this enzyme crucial to bacillithiol production. In addition, a time-conscious assay using a plate reader has been developed and characterized that may be used to test the efficacy of the identified potential inhibitors. This work is potentially useful to the design of an antibiotic-inhibitor “cocktail” that might be administered for infections currently untreatable by fosfomycin.

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