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Computer Simulation of the Virulome of Bacillus anthracis Using Proteomics
Final rept. 1 Apr 2005-31 Jul 2006
VITAL PROBES MAYFIELD PA
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Proteomic investigations of the biological warfare agent BWA Bacillus anthracis contributes to a comprehensive view of the cellular events that occur under host simulated conditions. The proteome of an organism is the sum of all proteins produced under defined conditions. It represents a global metabolic snapshot of a cell or microorganism at a particular moment. Presently there are large gaps in our knowledge about how B. anthracis infects and interacts with its host and how it causes its devastating consequences, what factors determine the host range, and the means by which B. anthracis invades host cells once it gains entry into the organism. Additionally, the contribution and interrelation of proteins encoded on each plasmid and the chromosome to the pathogenic process is currently unclear. To gain a detailed view of these virulent mechanisms results from investigations of various B. anthracis proteomes and subproteomes are used to create models of the pathogenic process. Furthermore the factors that determine host range as well as the dynamic changes associated with the release of secreted proteins secretome used by B. anthracis during invasion of the host were investigated. A time course analysis of the secretome and the identification of its key proteins were conducted using proteomics approaches. Subproteomic data of such global changes in the secretome were then used for computer simulations of the B. anthracis virulome. In addition, the subproteomes of B. anthracis that lack one of two plasmids pXO1, pXO2- pXO1-, pXO2 or both plasmids pXO1-, pXO2- were compared. Using host reception labeled columns fibronectin, heparin, etc we also determined which B. anthracis proteins may be responsible in host cell invasion. Eluates of captured proteins were analyzed by LC-MSMS to determine what pathogen proteins interact with specific receptins.
APPROVED FOR PUBLIC RELEASE