Bacterial Transformation of Eukaryotes: The Host Factors

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DESCRIPTION (provided by applicant): Fifteen to twenty percent of human cancers are caused by viral and bacterial pathogens, including papilloma viruses, the hepatitis B virus, the Epstein-Barr virus and the bacterium Heticoba cter pylon. Strikingly, these pathogens share features with A. tumefaciens, a bacterium that elicits cancerous tumors in plants, is capable of genetically transforming yeast, and is also an extremely facile experimental system. Many A. tumefaciens virulence genes are essential for both yeast and plant (host) cell transformation, suggesting the conservation host factors that participate in the transformation process. Thus, A. tumefaciens transformation of the yeast S. cerevisiae can provide an excellent model for understanding how infectious agents cause human malignancies. Although several A. tumefaciens virulence determinants have been identified, host cell factors essential for bacterial transformation have remained elusive. The primary objective of this study is to define host cell factors essential for bacterial transformation of eukaryotes. Using the yeast transformation system we developed, we have begun to identify yeast mutants altered in their sensitivity to A. tumefaciens transformation. Subsequent identification of the mutant genes responsible for the altered frequency of transformation phenotype effectively identifies the critical host factor participants. This novel approach should define a number of host factors essential for bacterial transformation of eukaryotes, thereby providing insights into the basic molecular mechanisms underlying infectious agent induced carcinomas.