The virulence and immunogenicity of Salmonella typhosa grown in continuous culture.

In recent years the technique for the continuous cultivation of microorganisms has been adapted for a variety of uses. Gerhart (1946) and Barnes and Dewey (1947) have reported on the advantage of continuous cultivation over conventional methods for obtaining increased yields of bacterial cells, and von Hofsten et al. (1953) have extended the method to the cultivation of fungi. Continuous cultivation techniques offer several advantages. In some instances, the formation of a given enzyme may be inhibited by a constituent of the growth medium. By employing continuous culture, it is possible to grow large amounts of bacterial cells in a medium containing such low concentrations of the inhibiting constituent that enzyme formation is unaffected (Cohn and Torriani, 1953). In addition, metabolic products which may block the formation of some enzymes do not accumulate under conditions of continuous growth (Monod, 1950). Workers in the field of microbial genetics have also employed continuous culture as a tool in the study of mutation (Novick and Szilard, 1950, 1951), while others (Bryson and Szybalski, 1952) have used a modification of the technique as a means of selecting bacterial mutants which are highly resistant to such substances as antibiotics. Continuous cultivation techniques may also be applicable to the production of bacterial vaccines where the advantage of obtaining large quantities of cells in a relatively short period is obvious. On the other hand, a shift in the bacterial population during continuous growth from one of high protective potency to one of reduced immunogenicity would restrict the usefulness of this method in the large-scale production of organisms for vaccines. It cannot be denied that the opportunity eists for mutation and selection during continuous growth. Therefore a study of the effects of growth in continuous culture on the stability of the virulence and immunogenicity of SalmoneUa typhosa was undertaken.