Summary of Invention
Multidrug-resistant bacteria represent a serious ongoing threat to global public health and are also potential agents of bioterrorism. New antibiotic strategies are urgently needed to combat such bacteria. The iron uptake systems of pathogenic bacteria represent a promising new therapeutic target. Pathogenic bacteria must acquire essential iron from the human host. To accomplish this, they produce natural products called siderophores. These small molecules have extremely high affinities for Fe(III) and are able to “steal” iron from host proteins such as transferrins, ferritin, and heme-containing proteins. Genetic evidence indicates that siderophore-deficient strains of many bacteria exhibit drastically reduced virulence and growth in cellular and animal models of infection. Thus, new drugs that inhibit siderophore biosynthesis may provide a critical new line of defense against bacterial infections.
Dr. Tan's and Dr. Quadri's laboratories have developed the lead compound 5'-O‑(N‑salicylsulfamoyl) adenosine (salicyl‑AMS) as the first inhibitor of siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis, the causative agents of tuberculosis and plague respectively. This compound targets salicylation enzymes that are required for siderophore production in these and other pathogenic bacteria. They have also demonstrated that this compound inhibits the growth of M. tuberculosis and Y. pestis. Thus, salicyl‑AMS and analogs thereof represent a promising new class of potential antibiotics to treat these and other bacterial infections.
Advantage - Application
- New compounds, antibiotics, with activity against multidrug-resistant bacteria that may be used in the affected population and in anti-bioterrorism.
- New molecular target that is different from the usual targets addressed by current antibiotics and unique to bacteria - it does not have a human ortholog.
U.S. patent application published: US2009/0170805
Kannan Krishnamurthy, PhD
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