Transcriptional activation of Salmonella typhimurium invasion genes by a member of the phosphorylated response-regulator superfamily.
The Salmonella typhimurium PhoP-repressed locus prgHIJK encodes components 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 secretion apparatus and some of its targets, SapB, SapC and SspD, are necessary for epithelial cell invasion. The transcription of many invasion genes, including prgHIJK, is coordinately activated by HilA, a transcription factor encoded within the pathogenicity island. In this report we identify sirA, a gene located outside the pathogenicity island that is essential for induction of prgHIJK and hilA transcription. sirA encodes a 234-amino-acid protein that is essential for S. typhimurium Ssp (Salmonella secreted protein) secretion and invasion and is similar to response regulators of two-component regulatory systems. sirA-mutant phenotypes could be suppressed by two DNA clones from unlinked loci, designated sirB and sirC. These data suggest that SirA may be phosphorylated in response to S. typhimurium sensing a mammalian microenvironment. Furthermore, SirA phosphorylation is predicted to initiate a cascade of transcription-factor synthesis which results in invasion-gene transcription, Ssp secretion, and bacterial invasion of epithelia.
Johnston
C
C
Department of Medicine, University of Washington, Seattle 98195, USA.
Pegues
D A
DA
Hueck
C J
CJ
Lee
A
A
Miller
S I
SI
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D004269:DNA, Bacterial; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D010766:Phosphorylation; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D001426:Bacterial Proteins; D004269:DNA, Bacterial; C102236:HilA protein, Salmonella; C079790:PrgH protein, Salmonella typhimurium; C104847:SirA protein, Salmonella; D015534:Trans-Activators