Effect of different plasmids on colonization of mouse tissues by the aromatic amino acid dependent Salmonella typhimurium SL 3261.

The stability of plasmids pBR322, pUC19 and pBluescript and their effect on bacterial colonization of mice was determined. S. typhimurium SL 3261 carrying high copy number plasmids colonized spleen and liver tissues poorly compared to low copy number plasmids. After inoculation into mice, the stability of the plasmids appeared to be inversely related to the plasmid's size and complexity. Mouse-passaging a pBluescript-based recombinant plasmid expressing the Protective Antigen of Bacillus anthracis selected for a mutant S. typhimurium strain (designated G3) that colonized at high levels and more stably maintained plasmids than S. typhimurium SL 3261. S. typhimurium G3 down-regulated the copy number of ColE1 plasmids. The significance of these data for vaccine design is discussed.