Synthesis of Modified Analogues of 3-deoxy-D-manno-octulosonic Acid (KDO) as Probes to Investigate the Donor Substrate Specificity of KDO Transferase

Abstract

There have always been reported cases of bacteria able to resist antibiotic treatment. Through recent history, infections with bacteria capable of resisting at least one type of drug treatment have become more commonplace [1,2,3]. The dearth of novel-acting antibiotics, combined with the resourcefulness of pathogenic bacteria under selective pressure means that humans are now faced with strains of bacteria that have developed resistance to multiple drugs. Of the few novel acting antibiotics developed in the last 30 years, most are targeted only to Gram positive bacteria, and reports of bacteria demonstrating resistance to these drugs have already surfaced [4,5,6]. The vast difference in the number of drugs available for treatment of Gram positive versus Gram negative bacterial infections is a direct reflection of the difficulty in targeting Gram negative bacteria with drugs. Drugs which treat Gram positive infections are often superfluous against Gram negative bacteria in large part due to the extra outer cell membrane these bacteria possess, which acts as an additional physical barrier and contains drug efflux pumps, ABC transporters and selective porins [7]. The structural integrity of the outer memberane structure has been shown to be essential to the viabililty of pathogenic Gram negative bacteria, which makes it an attractive target for the development of novel acting antibiotics [8].