Regulation of virulence gene expression in vivo

In this chapter, the invasion locus of serovar Typhimurium is used to exemplify several general points about the regulation of virulence gene expression in vivo. The chapter also includes a brief description of in vivo expression technology (IVET), designed to select for bacterial genes that are transcriptionally induced in the host. The regulation of invasion gene expression involves an increasingly large number of regulatory loci in addition to HilA and InvF. The original IVET system was based on the fact that purA mutants of serovar Typhimurium are completely incapable of surviving within the animal host. PurA is required at all stages of Salmonella infection in all host tissues. Researchers designed an analogous system using the chloramphenicol acetyl-transferase or cat gene as a reporter in place of purA . A number of researchers have subsequently developed IVET systems that are variations on a theme and have used these systems to identify in vivo-induced genes in a variety of both prokaryotic and eukaryotic pathogens. These IVET systems fall into three categories: (i) selection systems based on metabolic (e.g., purA ) or antibiotic (e.g., cat) reporters, (ii) recombination-based systems, and (iii) green fluourescent protein (GFP)-based systems. Approximately 10% of the genes that answered these selections encode products that are known or thought to be involved in serovar Typhimurium pathogenesis.