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        Fluorescence-Based Methods to Assay Inhibitors of Lipopolysaccharide Synthesis

        互联网

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        Treatment of infections caused by Gram-negative bacteria is difficult due in large part to problems arising from innate and acquired drug resistance, resulting in a limited number of effective antibiotics. Consequently, antibiotics that can circumvent mechanisms of drug resistance are needed. Lipid A is a glucosamine phospholipid that acts as an anchor for lipopolysaccharides (LPS) that comprise the outer membranes of Gram-negative bacteria, a barrier for small molecule entry into the cell, and is also the portion of LPS that stimulates the immune system in septic shock. Consequently, inhibitors of lipid A biosynthesis have the potential to function as antibiotics and/or anti-endotoxins in the treatment of Gram-negative bacterial infections. Current efforts in the development of antibiotics targeted against lipid A have focused on the metal-dependent deacetylase LpxC. Herein we describe fluorescence-based assays that can be used for the evaluation of LpxC inhibitors with the potential to serve as antibiotics.
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