BACTERIAL-INFECTION AS ASSESSED BY IN-VIVO GENE-EXPRESSION

In vivo expression technology (IVET) has been used to identify >100 Sa lmonella typhimurium genes that are specifically expressed during infe ction of BALB/c mice and/or murine cultured macrophages. Induction of these genes is shown to be required for survival in the animal under c onditions of the IVET selection. One class of in vivo induced (ivi) ge nes, iviVI-A and iviVI-B, constitute an operon that resides in a regio n of the Salmonella genome with low G+C content and presumably has bee n acquired by horizontal transfer, These ipi genes encode predicted pr oteins that are similar to adhesins and invasins from prokaryotic and eukaryotic pathogens (Escherichia coli [tia], Plasmodium falciparum [P fEMP1]) and have coopted the PhoPQ regulatory circuitry of Salmonella virulence genes. Examination of the in vivo induction profile indicate s (i) many ivi genes encode regulatory functions (e.g., phoPQ and pmrA B) that serve to enhance the sensitivity and amplitude of virulence ge ne expression (e.g., spvB); (ii) the biochemical function of many meta bolic genes may not represent their sole contribution to virulence; (i ii) the host ecology can be inferred from the biochemical functions of ipi genes; and (iv) nutrient limitation plays a dual signaling role i n pathogenesis: to induce metabolic functions that complement host nut ritional deficiencies and to induce virulence functions required for i mmediate survival and spread to subsequent host sites.