HILA IS A NOVEL OMPR TOXR FAMILY MEMBER THAT ACTIVATES THE EXPRESSIONOF SALMONELLA-TYPHIMURIUM INVASION GENES/

During infection of its hosts, Salmonella enters intestinal epithelial cells. Many Salmonella typhimurium genes required for bacterial entry into host cells are encoded on a 40 kb 'pathogenicity island'. We rep ort here the identification of hilA, a gene within the 'island' that a ppears to encode an activator of invasion gene expression. By using a set of lacZY transcriptional fusions to S. typhimurium invasion genes, we found that hilA activates the expression of invasion genes located on the 'pathogenicity island'. hilA is required for efficient entry i nto HEp-2 cells in vitro. The predicted amino acid sequence of hilA sh ares significant homology with the DNA-binding domains of the OmpR-Tox R family of transcriptional activators. However, unlike OmpR and ToxR, HilA contains neither a phosphoryl acceptor nor a membrane-spanning d omain, and, therefore, its activity may be modulated by a novel mechan ism. Many environmental conditions modulate the ability of Salmonella to enter non-phagocytic mammalian cells. It has been proposed that ind uction of Salmonella invasion proteins in response to a combination of environmental cues ensures that bacterial entry is limited to specifi c sites and times during infection. Our results are consistent with th e hypothesis that hilA plays a key role in the regulation of Salmonell a invasion during infection.