title: Rational design of an artificial genetic switch: Co-option of the H-NS-repressed proU operon by the VirB virulence master regulator.
abstract: The H-NS protein represses the transcription of hundreds of genes in Gram-negative bacteria. Derepression is achieved by a multitude of mechanisms, many of which involve the binding of a protein to DNA at the repressed promoter in a manner that compromises the maintenance of the H-NS-DNA nucleoprotein repression complex. The principal virulence gene promoters in Shigella flexneri, the cause of bacillary dysentery, are repressed by H-NS. VirB, a protein that closely resembles members of the ParB family of plasmid-partitioning proteins, derepresses the operons that encode the main structural components and the effector proteins of the S. flexneri type III secretion system. Bioinformatic analysis suggests that VirB has been co-opted into its current role as an H-NS antagonist in S. flexneri. To test this hypothesis, the potential for VirB to act as a positive regulator of proU, an operon that is repressed by H-NS, was assessed. Although VirB has no known relationship with the osmoregulated proU operon, it could relieve H-NS-mediated repression when the parS-like VirB binding site was placed appropriately upstream of the RpoD-dependent proU promoter. These results reveal the remarkable facility with which novel regulatory circuits can evolve, at least among those promoters that are repressed by H-NS.
authors.affiliation: Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Kane
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Dorman
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D009876:Operon; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D012763:Shigella flexneri / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D026905:Amino Acid Transport Systems; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C031908:H-NS protein, bacteria; C060774:ProU protein, Bacteria; D014157:Transcription Factors; D037521:Virulence Factors