title: A small protein that mediates the activation of a two-component system by another two-component system.
abstract: The PmrA-PmrB two-component system of Salmonella enterica controls resistance to the peptide antibiotic polymyxin B and to several antimicrobial proteins from human neutrophils. Transcription of PmrA-activated genes is induced by high iron, but can also be promoted by growth in low magnesium in a process that requires another two-component system, PhoP-PhoQ. Here, we define the genetic basis for the interaction between the PhoP-PhoQ and PmrA-PmrB systems. We have identified pmrD as a PhoP-activated gene that mediates the transcriptional activation of PmrA-regulated genes during growth in low magnesium. When transcription of pmrD is driven from a heterologous promoter, expression of PmrA-activated genes occurs even at repressing magnesium concentrations and becomes independent of the phoP and phoQ genes. The PmrD effect is specific for PmrA-regulated genes and requires functional PmrA and PmrB proteins. A pmrD mutant is sensitive to polymyxin if grown in low magnesium, but resistant if grown in high iron. The PmrD protein controls the activity of the PmrA-PmrB system at a post-transcriptional level.
authors.affiliation: Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110-1093, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Kox
authors.forename: M M
authors.initials: MM
authors.lastname: Wösten
authors.forename: E A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004352:Drug Resistance, Microbial; D007501:Iron / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids; D011113:Polymyxins / Q000378:metabolism; D011485:Protein Binding; D012323:RNA Processing, Post-Transcriptional; D011994:Recombinant Proteins / Q000378:metabolism; D019779:Salmonella enterica / Q000737:chemistry*; D015398:Signal Transduction; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C079792:PhoQ protein, Bacteria; C409039:PmrB protein, bacteria; D011113:Polymyxins; D011994:Recombinant Proteins; D014157:Transcription Factors; C081902:pmrA protein, Bacteria; C061064:PhoP protein, Bacteria; D007501:Iron; D015719:Single-Strand Specific DNA and RNA Endonucleases; D008274:Magnesium