TRANSCRIPTIONAL ACTIVATION OF SALMONELLA-TYPHIMURIUM INVASION GENES BY A MEMBER OF THE PHOSPHORYLATED RESPONSE-REGULATOR SUPERFAMILY

The Salmonella typhimurium PhoP-repressed locus prgHIJK encodes compon ents of a sec-independent type III secretion apparatus. This apparatus is composed of at least 17 proteins encoded on a 40 kb pathogenicity island located at centisome 63 on the S. typhimurium chromosome. The s ecretion apparatus and some of its targets, SspB, SspC and SspD, are n ecessary for epithelial cell invasion. The transcription of many invas ion genes, including prgHIJK, is coordinately activated by HilA, a tra nscription factor encoded within the pathogenicity island. In this rep ort we identify sirA, a gene located outside the pathogenicity island that is essential for induction of prgHIJK and hilA transcription, sir A encodes a 234-amino-acid protein that is essential for S. typhimuriu m Ssp (Salmonella secreted protein) secretion and invasion and is simi lar to response regulators of two-component regulatory systems, sirA-m utant phenotypes could be suppressed by two DNA clones from unlinked l oci, designated sirB and sirC, These data suggest that SirA may be pho sphorylated in response to S. typhimurium sensing a mammalian microenv ironment. Furthermore, SirA phosphorylation is predicted to initiate a cascade of transcription-factor synthesis which results in invasion-g ene transcription, Ssp secretion, and bacterial invasion of epithelia.