A selection strategy was devised to identify bacterial genes preferent
ially expressed when a bacterium associates with its host cell. Fourte
en Salmonella typhimurium genes, which were under the control of at le
ast four independent regulatory circuits, were identified to be select
ively induced in host macrophages. Four genes encode virulence factors
, including a component of a type III secretory apparatus. This select
ion methodology should be generally applicable to the identification o
f genes from pathogenic organisms that are induced upon association wi
th host cells or tissues.