Use of mixed infections with Salmonella strains to study virulence genes and their interactions in vivo.

In the Salmonella-mouse model of systemic infection, high dose inoculation results in the multiplication of many of the cells present in the inoculum, rather than the clonal amplification of a small number. This characteristic has allowed the development of methods to screen multiple strains for either virulence attenuation or gene expression within the same animal. Mixed infections with mutant and wild-type strains are used to provide a sensitive measure of virulence attenuation referred to as the competitive index. We have recently used a variation of this method, involving mixed infections of single and double mutant strains, to study virulence gene interaction in vivo.