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PMID: 10775270 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

A small protein that mediates the activation of a two-component system by another two-component system.

The EMBO journal ·Vol. 19 ·No. 8 ·2000-04-17 ·Pages 1861-72

Kox LF, Wösten MM, Groisman EA

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.

MeSH Terms
Anti-Bacterial Agents/metabolism Bacterial Proteins/genetics,metabolism Base Sequence Drug Resistance, Microbial Iron/metabolism Magnesium/metabolism Models, Biological Molecular Sequence Data Mutagenesis Mutation Phosphorylation Plasmids Polymyxins/metabolism Protein Binding RNA Processing, Post-Transcriptional Recombinant Proteins/metabolism Salmonella enterica/chemistry Signal Transduction Single-Strand Specific DNA and RNA Endonucleases/metabolism Transcription Factors/genetics,metabolism Transcription, Genetic
Chemicals
Anti-Bacterial Agents Bacterial Proteins PhoQ protein, Bacteria PmrB protein, bacteria Polymyxins Recombinant Proteins Transcription Factors pmrA protein, Bacteria PhoP protein, Bacteria Iron Single-Strand Specific DNA and RNA Endonucleases Magnesium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kox L F
Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110-1093, USA.
Wösten M M
Groisman E A
References (36)
36 references, click to expand
  1. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors.
    Gene. 1985;33(1):103-19 PMID: 2985470
  2. Molecular characterization of the PmrA regulon.
    J Biol Chem. 1999 Sep 17;274(38):27185-90 PMID: 10480935
  3. A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells.
    Science. 1989 Feb 24;243(4894 Pt 1):1059-62 PMID: 2646710
  4. Salmonella typhimurium phoP virulence gene is a transcriptional regulator.
    Proc Natl Acad Sci U S A. 1989 Sep;86(18):7077-81 PMID: 2674945
  5. Protein phosphorylation and regulation of adaptive responses in bacteria.
    Microbiol Rev. 1989 Dec;53(4):450-90 PMID: 2556636
  6. Phosphorylation and dephosphorylation of a bacterial transcriptional activator by a transmembrane receptor.
    Genes Dev. 1989 Nov;3(11):1725-34 PMID: 2558046
  7. The mgtB Mg2+ transport locus of Salmonella typhimurium encodes a P-type ATPase.
    J Biol Chem. 1991 Jan 15;266(2):815-23 PMID: 1824701
  8. Is cross regulation by phosphorylation of two-component response regulator proteins important in bacteria?
    J Bacteriol. 1992 Apr;174(7):2053-8 PMID: 1551826
  9. Molecular, functional, and evolutionary analysis of sequences specific to Salmonella.
    Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1033-7 PMID: 8430070
  10. Spontaneous pmrA mutants of Salmonella typhimurium LT2 define a new two-component regulatory system with a possible role in virulence.
    J Bacteriol. 1993 Jul;175(13):4154-64 PMID: 8391535
  11. Isolation and characterization of a gene, pmrD, from Salmonella typhimurium that confers resistance to polymyxin when expressed in multiple copies.
    J Bacteriol. 1994 Jun;176(12):3589-97 PMID: 8206837
  12. Genetic map of Salmonella typhimurium, edition VIII.
    Microbiol Rev. 1995 Jun;59(2):241-303 PMID: 7603411
  13. Transcriptional autoregulation of the Salmonella typhimurium phoPQ operon.
    J Bacteriol. 1995 Aug;177(15):4364-71 PMID: 7543474
  14. New plasmids carrying antibiotic-resistance cassettes.
    Gene. 1995 Nov 7;165(1):141-2 PMID: 7489905
  15. Mg2+ as an extracellular signal: environmental regulation of Salmonella virulence.
    Cell. 1996 Jan 12;84(1):165-74 PMID: 8548821
  16. Molecular basis of the magnesium deprivation response in Salmonella typhimurium: identification of PhoP-regulated genes.
    J Bacteriol. 1996 Sep;178(17):5092-9 PMID: 8752324
  17. Protein aspartate phosphatases control the output of two-component signal transduction systems.
    Trends Genet. 1996 Mar;12(3):97-101 PMID: 8868347
  18. Signal detection by the PhoQ sensor-transmitter. Characterization of the sensor domain and a response-impaired mutant that identifies ligand-binding determinants.
    J Biol Chem. 1996 Oct 25;271(43):26630-6 PMID: 8900137
  19. Two-component regulatory systems can interact to process multiple environmental signals.
    J Bacteriol. 1996 Dec;178(23):6796-801 PMID: 8955299
  20. PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance.
    J Bacteriol. 1996 Dec;178(23):6857-64 PMID: 8955307
  21. Characterization of the bacterial sensor protein PhoQ. Evidence for distinct binding sites for Mg2+ and Ca2+.
    J Biol Chem. 1997 Jan 17;272(3):1440-3 PMID: 8999810
  22. Signal transduction pathways in response to protein misfolding in the extracytoplasmic compartments of E. coli: role of two new phosphoprotein phosphatases PrpA and PrpB.
    EMBO J. 1997 Apr 1;16(7):1670-85 PMID: 9130712
  23. Histidine kinases in signal transduction pathways of eukaryotes.
    J Cell Sci. 1997 May;110 ( Pt 10):1141-5 PMID: 9191038
  24. Regulation of polymyxin resistance and adaptation to low-Mg2+ environments.
    J Bacteriol. 1997 Nov;179(22):7040-5 PMID: 9371451
  25. An Escherichia coli protein that exhibits phosphohistidine phosphatase activity towards the HPt domain of the ArcB sensor involved in the multistep His-Asp phosphorelay.
    Mol Microbiol. 1998 Feb;27(3):573-85 PMID: 9489669
  26. PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance.
    Mol Microbiol. 1998 Mar;27(6):1171-82 PMID: 9570402
  27. Pho signal transduction network reveals direct transcriptional regulation of one two-component system by another two-component regulator: Bacillus subtilis PhoP directly regulates production of ResD.
    Mol Microbiol. 1998 Dec;30(5):943-53 PMID: 9988472
  28. Two-component signal transduction in Bacillus subtilis: how one organism sees its world.
    J Bacteriol. 1999 Apr;181(7):1975-83 PMID: 10094672
  29. Signalling pathways in two-component phosphorelay systems.
    Trends Microbiol. 1999 Mar;7(3):115-20 PMID: 10203840
  30. Molecular characterization of the PhoP-PhoQ two-component system in Escherichia coli K-12: identification of extracellular Mg2+-responsive promoters.
    J Bacteriol. 1999 Sep;181(17):5516-20 PMID: 10464230
  31. OmpR regulates the two-component system SsrA-ssrB in Salmonella pathogenicity island 2.
    J Bacteriol. 2000 Feb;182(3):771-81 PMID: 10633113
  32. Isolation and characterization of a mutant of Salmonella typhimurium deficient in a major deoxyribonucleic acid polymerase activity.
    J Bacteriol. 1973 Oct;116(1):54-8 PMID: 4355486
  33. Studies on transformation of Escherichia coli with plasmids.
    J Mol Biol. 1983 Jun 5;166(4):557-80 PMID: 6345791
  34. Lipid A and resistance of Salmonella typhimurium to antimicrobial granule proteins of human neutrophil granulocytes.
    Infect Immun. 1984 Mar;43(3):834-8 PMID: 6199303
  35. Cationic antimicrobial proteins isolated from human neutrophil granulocytes in the presence of diisopropyl fluorophosphate.
    Infect Immun. 1984 Jul;45(1):29-35 PMID: 6376359
  36. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent.
    Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189-93 PMID: 3523484
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.8.1861
Published
2000-04-17
Pages
1861-72
Language
English
Region
England
NLM ID
8208664
PMCID
PMC302009
Subset
IM
Grants
NIAID NIH HHS · R01 AI042236 · United States
NIAID NIH HHS · R56 AI042236 · United States
NIAID NIH HHS · AI42236 · United States
External Links
PubMed source DOI: 10.1093/emboj/19.8.1861 PMC Full Text View journal details
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