Bacterial infection as assessed by in vivo gene expression

Abstract

In vivo e xpression t echnology (IVET) has been used to identify >100 Salmonella typhimurium genes that are specifically expressed during infection of BALB/c mice and/or murine cultured macrophages. Induction of these genes is shown to be required for survival in the animal under conditions of the IVET selection. One class of in vivo i nduced ( ivi ) genes, iviVI-A and iviVI-B , constitute an operon that resides in a region of the Salmonella genome with low G+C content and presumably has been acquired by horizontal transfer. These ivi genes encode predicted proteins that are similar to adhesins and invasins from prokaryotic and eukaryotic pathogens ( Escherichia coli [ tia ], Plasmodium falciparum [PfEMP1]) and have coopted the PhoPQ regulatory circuitry of Salmonella virulence genes. Examination of the in vivo induction profile indicates ( i ) many ivi genes encode regulatory functions (e.g., phoPQ and pmrAB ) that serve to enhance the sensitivity and amplitude of virulence gene expression (e.g., spvB ); ( ii ) the biochemical function of many metabolic genes may not represent their sole contribution to virulence; ( iii ) the host ecology can be inferred from the biochemical functions of ivi genes; and ( iv ) nutrient limitation plays a dual signaling role in pathogenesis: to induce metabolic functions that complement host nutritional deficiencies and to induce virulence functions required for immediate survival and spread to subsequent host sites.