INDUCTION OF THE PHOE PROMOTER UPON INVASION OF SALMONELLA-TYPHIMURIUM INTO EUKARYOTIC CELLS

Live attenuated Salmonella typhimurium strains expressing foreign anti gens can be used for vaccination purposes. Due to deleterious effects of constitutive, high-level expression of the heterologous antigens, t here is often strong selection pressure against plasmids encoding thes e antigens, resulting in rapid segregation in vivo. In vivo-inducible promoters may be a good alternative for constitutive promoters. The ou ter membrane protein PhoE of Escherichia coli is being used as a carri er for foreign antigenic determinants. Here we studied whether its exp ression from a plasmid is induced in S. typhimurium upon invasion of e ukaryotic cells. This appeared to be the case. Furthermore, a S. typhi murium phoE mutant was constructed and the effects of the mutation on invasion, intracellular survival and virulence were studied. Survival in HEp-2 cells or in the macrophage-like cell line J744 was not, or on ly slightly, affected. Furthermore, the mutant appeared to be as virul ent for mice as the wild-type strain. (C) 1995 Academic Press Limited