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Our group investigates models for the first hours of anthrax infections, in vivo germination of theBacillus anthracis endospore, macrophage survival, growth and escape of the vegetative bacilli into the blood. Outside the host, endospores remain metabolically-dormant, preserving virulence even when exposed to harsh environmental conditions. Endospores are the anthrax contagion, entering the body where they are phagocytosed by regional macrophages. Endospores "sense" the new locale, germinate and outgrow to a vegetative state. After escape, massive bacteremia, toxemia and death ensue. We are examining each of these stages and defining discrete mutants blocked at each step. Our data indicate that anthrax endospores have unique in vivo sensory and signalling mechanisms for triggering germination. Germination occurs rapidly in cultured macrophages. Non-pathogenic Bacillus sp. endospores show no increased germination in macrophages. B. anthracistransposon-mediated mutagenesis systems and directed knock-outs allow selection of individual endospore mutants incapable of germination in macrophages but fully capable of germination and outgrowth in bacterial media, the identification of genes involved in the intracellular events of bacterial growth, including new toxin genes. We employ, as experimental tools, methods of molecular pathogenesis, functional genomics and functional proteomics.
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Daniel D. Sommer,Shashikala Ratnayake,Diana Radune,Kisha Parker, Sana Enke, Tracy M. Ferguson, Marie Lovett, Adam Mallonee, Zach Rae,M. J. Rosovitz, Lynn F. Diviak, Mary Beth Friss,
Ada K. Hagan, Yael M. Plotnick, Ryan E. Dingle, Zachary I. Mendel, Stephen R. Cendrowski,David H. Sherman,Ashootosh Tripathi,Philip C. Hanna
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