Development of Antibacterials Targeting the MEP Pathway of Select Agents.

摘要

The threat of bioterrorism and the use of biological weapons against both military personnel and civilian populations has become an increasing concern for governments around the world. The 1984 Rajneeshee Salmonella attack, 2001 anthrax letter attacks, 2003 SARS outbreak, 2009 H1N1 swine flu pandemic, and the current US flu epidemic all illustrate our vulnerability to both deliberate and natural outbreaks of infectious disease and underscore the necessity of effective antimicrobial and antiviral therapeutics. The prevalence of antibiotic resistant strains and the ease by which antibiotic resistance can be engineered into bacteria further highlights the need for continued development of novel antibiotics against new bacterial targets. This research project directly addresses this need through the development of a broad spectrum inhibitor of the biothreat agents Francisella tularensis and Yersinia pestis. During this period of performance, we have utilized our optimized assays with the Y. pestis MEP synthase and the F. tularensis MEP cytidylyltransferase to screen molecular libraries and identify effective inhibitors of both MEP synthase and MEP cytidylyltransferase.