title: Regulation of enteric vapBC transcription: induction by VapC toxin dimer-breaking.
abstract: Toxin-antitoxin (TA) loci encode inhibitors of translation, replication or cell wall synthesis and are common elements of prokaryotic plasmids and chromosomes. Ten TA loci of Escherichia coli K-12 encode mRNases that cumulatively contribute to persistence (multidrug tolerance) of the bacterial cells. The mechanisms underlying induction and reversion of the persistent state are not yet understood. The vapBC operon of Salmonalla enterica serovar Typhimurium LT2 encodes VapC, a tRNase that reversibly inhibits translation by site-specific cleavage of tRNA(fMet). VapB is an antitoxin that interacts with and neutralizes VapC via its C-terminal tail and regulate TA operon transcription via its N-terminal DNA binding domain that recognize operators in the vapBC promoter region. We show here that transcription of the vapBC operon of S. enterica is controlled by a recently discovered regulatory theme referred to as 'conditional cooperativity': at low T/A ratios, the TA complex binds cooperatively to the promoter region and represses TA operon transcription whereas at high T/A ratios, the excess toxin leads to destabilization of the TA-operator complex and therefore, induction of transcription. We present evidence that an excess of VapC toxin leads to operator complex destabilization by breaking of toxin dimers.
authors.affiliation: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, NE2 4AX Newcastle, UK.
authors.forename: Kristoffer S
authors.initials: KS
authors.lastname: Winther
authors.forename: Kenn
authors.initials: K
authors.lastname: Gerdes
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009154:Mutation; D009875:Operator Regions, Genetic; D009876:Operon; D049070:Protease La / Q000378:metabolism; D011485:Protein Binding; D012260:Ribonucleases / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; C077517:VapB protein, Bacteria; D012260:Ribonucleases; D049070:Protease La