title: The flagellar regulator fliT represses Salmonella pathogenicity island 1 through flhDC and fliZ.
abstract: Salmonella pathogenicity island 1 (SPI1), comprising a type III section system that translocates effector proteins into host cells, is essential for the enteric pathogen Salmonella to penetrate the intestinal epithelium and subsequently to cause disease. Using random transposon mutagenesis, we found that a Tn10 disruption in the flagellar fliDST operon induced SPI1 expression when the strain was grown under conditions designed to repress SPI1, by mimicking the environment of the large intestine through the use of the intestinal fatty acid butyrate. Our genetic studies showed that only fliT within this operon was required for this effect, and that exogenous over-expression of fliT alone significantly reduced the expression of SPI1 genes, including the invasion regulator hilA and the sipBCDA operon, encoding type III section system effector proteins, and Salmonella invasion of cultured epithelial cells. fliT has been known to inhibit the flagellar machinery through repression of the flagellar master regulator flhDC. We found that the repressive effect of fliT on invasion genes was completely abolished in the absence of flhDC or fliZ, the latter previously shown to induce SPI1, indicating that this regulatory pathway is required for invasion control by fliT. Although this flhDC-fliZ pathway was necessary for fliT to negatively control invasion genes, fliZ was not essential for the repressive effect of fliT on motility, placing fliT high in the regulatory cascade for both invasion and motility.
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, New York, United States of America.
authors.forename: Chien-Che
authors.initials: CC
authors.lastname: Hung
authors.forename: Leanne
authors.initials: L
authors.lastname: Haines
authors.forename: Craig
authors.initials: C
authors.lastname: Altier
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D001435:Bacteriophages / Q000235:genetics; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D004251:DNA Transposable Elements; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000235:genetics*; D009068:Movement; D016296:Mutagenesis; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D012475:Salmonella / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D012480:Salmonella Infections / Q000235:genetics / Q000382:microbiology; D015534:Trans-Activators / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D018832:Molecular Chaperones; D015534:Trans-Activators; C076735:fliT protein, Bacteria; D001616:beta-Galactosidase