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 effe ct on bacterial colonization of mice was determined. S. typhimurium SL 3261 carrying high copy number plasmids colonized spleen and liver ti ssues poorly compared to low copy number plasmids. After inoculation i nto mice, the stability of the plasmids appeared to be inversely relat ed to the plasmid's size and complexity. Mouse-passaging a pBluescript -based recombinant plasmid expressing the Protective Antigen of Bacill us anthracis selected for a mutant S. typhimurium strain (designated G 3) that colonized at high levels and more stably maintained plasmids t han S. typhimurium SL 3261. S. typhimurium G3 down-regulated the copy number of ColE1 plasmids. The significance of these data for vaccine d esign is discussed.