The potential for the use of a biological weapon of mass destruction by terrorist groups or rogue nations has increased dramatically since the collapse of the Soviet Union. Bioweapons are no longer contained within the bounds of the cold war arsenals. They are cheap, easy to make, and easy to use. Burkholderia mallei, one of the organisms used by the Soviets in their bioweapons program, possesses properties which contribute to its potential as a biological weapon. The disease, glanders, can result from an extremely low infectious dose inoculated by either aerosol, oral, or parental routes. The incubation period is short and no effective vaccine is available. Definitive diagnosis of glanders is confounded by nonspecific signs and symptoms. Although glanders is a serious life-threatening zoonotic disease, relatively little is known about the pathogenesis, virulence factors, strain differences, and the host immunopathologic responses to infection. Antibiotic therapy is unreliable. The specific aims of this proposal are therefore to: Determine the complete DNA sequence of the approximately 6.5 Mb Burkholderia mallei genome, analyze and annotate the genome sequence, and make the sequence and analysis data available to the research community. At TIGR, we have accomplished the complete genomic sequencing of 18 microbial organisms. The infrastructure we have built and the protocols we have developed assure that our sequencing of this organism will provide the highest quality sequence at the lowest cost. The availability of the complete B. mallei annotated genome sequence will be instrumental for the success of studies on the pathogenicity of this organism and will be crucial to efforts to develop effective diagnostics, vaccines, and therapies.