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PMID: 16625355 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Rhizobium leguminosarum regulator IrrA affects the transcription of a wide range of genes in response to Fe availability.

Molecular genetics and genomics : MGG ·Vol. 275 ·No. 6 ·2006-06-00 ·Pages 564-77

Todd JD, Sawers G, Rodionov DA, Johnston AW

Abstract

We show that an unusual transcriptional regulator, called IrrA, regulates many genes in the symbiotic N2-fixing bacterium Rhizobium leguminosarum in response to iron availability. Several operons in R. leguminosarum are expressed at lower levels in cells grown in Fe-depleted compared to Fe-replete medium. These include hemA1, which encodes the haem biosynthesis enzyme amino-levulinic acid synthase; sufS2BCDS1XA, which specify enzymes for FeS cluster synthesis; rirA, a global, Fe-responsive transcriptional repressor; RL0400, which likely encodes an unusual FeS cluster scaffold; and the possible ferri-siderophore ABC transporter rrp1. Reduced expression in Fe-depleted medium was effected by IrrA, a member of the Fur super-family, which in Bradyrhizobium, the symbiont of soybeans, and in the mammalian pathogen Brucella, is unstable in Fe-replete conditions, due to an interaction with haem. The R. leguminosarum IrrA likely interacts with ICE (iron-control element) motifs, conserved sequences near the promoters of its target genes. The rirA, sufS2BCDS1XA and rrp1 genes are also known to be regulated by RirA, which represses their expression in Fe-replete medium. We present a possible model for iron-responsive gene regulation in Rhizobium, in which the IrrA and RirA regulators, working in parallel, respond to the intracellular availability of haem and, possibly, of FeS clusters respectively. Thus, these regulators may sense the physiological consequences of extraneous Fe concentrations, rather than the concentration of Fe per se, as happens in those bacteria (e.g. Escherichia coli) in which the ferric uptake regulator Fur is the global Fe-responsive gene regulator.

MeSH Terms
Bacterial Proteins/genetics,physiology Base Sequence DNA Primers Heme/biosynthesis Mutagenesis, Site-Directed Mutation Rhizobium leguminosarum/genetics Transcription, Genetic/physiology
Chemicals
Bacterial Proteins DNA Primers Heme
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Todd Jonathan D
School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich, UK.
Sawers Gary
Rodionov Dmitry A
Johnston Andrew W B
References (55)
55 references, click to expand
  1. Heme biosynthesis in Rhizobium. Identification of a cloned gene coding for delta-aminolevulinic acid synthetase from Rhizobium meliloti.
    J Biol Chem. 1982 Aug 10;257(15):8724-30 PMID: 7096330
  2. Comparative analysis of FUR regulons in gamma-proteobacteria.
    Nucleic Acids Res. 2001 Dec 15;29(24):5195-206 PMID: 11812853
  3. Computer analysis of transcription regulatory patterns in completely sequenced bacterial genomes.
    Nucleic Acids Res. 1999 Jul 15;27(14):2981-9 PMID: 10390542
  4. Prediction of transcription regulatory sites in Archaea by a comparative genomic approach.
    Nucleic Acids Res. 2000 Feb 1;28(3):695-705 PMID: 10637320
  5. Fur is involved in manganese-dependent regulation of mntA (sitA) expression in Sinorhizobium meliloti.
    Appl Environ Microbiol. 2004 Jul;70(7):4349-55 PMID: 15240318
  6. Analysis of the Rhizobium leguminosarum siderophore-uptake gene fhuA: differential expression in free-living bacteria and nitrogen-fixing bacteroids and distribution of an fhuA pseudogene in different strains.
    Microbiology (Reading). 2000 Apr;146 ( Pt 4):829-837 PMID: 10784041
  7. Discovery of a haem uptake system in the soil bacterium Bradyrhizobium japonicum.
    Mol Microbiol. 2001 Aug;41(4):787-800 PMID: 11532144
  8. RirA is the iron response regulator of the rhizobactin 1021 biosynthesis and transport genes in Sinorhizobium meliloti 2011.
    FEMS Microbiol Lett. 2005 May 15;246(2):235-42 PMID: 15899411
  9. The Fur-like protein Mur of Rhizobium leguminosarum is a Mn(2+)-responsive transcriptional regulator.
    Microbiology (Reading). 2004 May;150(Pt 5):1447-1456 PMID: 15133106
  10. Modular organization and identification of a mononuclear iron-binding site within the NifU protein.
    J Biol Inorg Chem. 2000 Apr;5(2):167-77 PMID: 10819462
  11. The vbs genes that direct synthesis of the siderophore vicibactin in Rhizobium leguminosarum: their expression in other genera requires ECF sigma factor RpoI.
    Mol Microbiol. 2002 Jun;44(5):1153-66 PMID: 12028377
  12. The Rhizobium leguminosarum tonB gene is required for the uptake of siderophore and haem as sources of iron.
    Mol Microbiol. 2001 Aug;41(4):801-16 PMID: 11532145
  13. Host specificity of DNA produced by Escherichia coli: bacterial mutations affecting the restriction and modification of DNA.
    J Mol Biol. 1966 Mar;16(1):118-33 PMID: 5331240
  14. Conformational changes of the ferric uptake regulation protein upon metal activation and DNA binding; first evidence of structural homologies with the diphtheria toxin repressor.
    J Mol Biol. 2001 Jun 29;310(1):83-91 PMID: 11419938
  15. Evidence that the Rhizobium regulatory protein RirA binds to cis-acting iron-responsive operators (IROs) at promoters of some Fe-regulated genes.
    Microbiology (Reading). 2004 Dec;150(Pt 12):4065-74 PMID: 15583159
  16. Heme binds to a short sequence that serves a regulatory function in diverse proteins.
    EMBO J. 1995 Jan 16;14(2):313-20 PMID: 7835342
  17. A suf operon requirement for Fe-S cluster assembly during iron starvation in Escherichia coli.
    Mol Microbiol. 2004 May;52(3):861-72 PMID: 15101990
  18. Evolutionary trees from DNA sequences: a maximum likelihood approach.
    J Mol Evol. 1981;17(6):368-76 PMID: 7288891
  19. Recognition of DNA by three ferric uptake regulator (Fur) homologs in Bacillus subtilis.
    J Bacteriol. 2003 Nov;185(21):6348-57 PMID: 14563870
  20. The Pfam protein families database.
    Nucleic Acids Res. 2002 Jan 1;30(1):276-80 PMID: 11752314
  21. Identification of a DtxR-regulated operon that is essential for siderophore-dependent iron uptake in Corynebacterium diphtheriae.
    J Bacteriol. 2002 Sep;184(17):4846-56 PMID: 12169610
  22. IscR, an Fe-S cluster-containing transcription factor, represses expression of Escherichia coli genes encoding Fe-S cluster assembly proteins.
    Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14895-900 PMID: 11742080
  23. Interaction between the bacterial iron response regulator and ferrochelatase mediates genetic control of heme biosynthesis.
    Mol Cell. 2002 Jan;9(1):155-62 PMID: 11804594
  24. R factor transfer in Rhizobium leguminosarum.
    J Gen Microbiol. 1974 Sep;84(1):188-98 PMID: 4612098
  25. Induction of the sufA operon encoding Fe-S assembly proteins by superoxide generators and hydrogen peroxide: involvement of OxyR, IHF and an unidentified oxidant-responsive factor.
    Mol Microbiol. 2004 Mar;51(6):1745-55 PMID: 15009899
  26. Identification of human and mouse HIRA-interacting protein-5 (HIRIP5), two mammalian representatives in a family of phylogenetically conserved proteins with a role in the biogenesis of Fe/S proteins.
    Biochim Biophys Acta. 2001 Feb 16;1517(3):376-83 PMID: 11342215
  27. Fur functions as an activator and as a repressor of putative virulence genes in Neisseria meningitidis.
    Mol Microbiol. 2004 May;52(4):1081-90 PMID: 15130126
  28. The manganese-responsive repressor Mur of Rhizobium leguminosarum is a member of the Fur-superfamily that recognizes an unusual operator sequence.
    Microbiology (Reading). 2005 Dec;151(Pt 12):4071-4078 PMID: 16339952
  29. The small RNA regulators of Escherichia coli: roles and mechanisms*.
    Annu Rev Microbiol. 2004;58:303-28 PMID: 15487940
  30. Fur is not the global regulator of iron uptake genes in Rhizobium leguminosarum.
    Microbiology (Reading). 2003 May;149(Pt 5):1357-1365 PMID: 12724397
  31. Fur-independent regulation of iron metabolism by Irr in Bradyrhizobium japonicum.
    Microbiology (Reading). 2000 Mar;146 ( Pt 3):669-676 PMID: 10746770
  32. Replication of an origin-containing derivative of plasmid RK2 dependent on a plasmid function provided in trans.
    Proc Natl Acad Sci U S A. 1979 Apr;76(4):1648-52 PMID: 377280
  33. Two heme binding sites are involved in the regulated degradation of the bacterial iron response regulator (Irr) protein.
    J Biol Chem. 2005 Mar 4;280(9):7671-6 PMID: 15613477
  34. Dimeric Brucella abortus Irr protein controls its own expression and binds haem.
    Microbiology (Reading). 2005 Oct;151(Pt 10):3427-3433 PMID: 16207924
  35. Effect of iron availability on expression of the Bradyrhizobium japonicum hemA gene.
    J Bacteriol. 1994 Mar;176(5):1535-8 PMID: 8113199
  36. GenBank.
    Nucleic Acids Res. 2005 Jan 1;33(Database issue):D34-8 PMID: 15608212
  37. The fhu genes of Rhizobium leguminosarum, specifying siderophore uptake proteins: fhuDCB are adjacent to a pseudogene version of fhuA.
    Microbiology (Reading). 1999 Mar;145 ( Pt 3):593-601 PMID: 10217493
  38. RirA, an iron-responsive regulator in the symbiotic bacterium Rhizobium leguminosarum.
    Microbiology (Reading). 2002 Dec;148(Pt 12):4059-4071 PMID: 12480909
  39. Expression of the iron-responsive irpA gene from the cyanobacterium Synechococcus sp strain PCC 7942.
    Arch Microbiol. 2003 Jan-Feb;179(2):131-4 PMID: 12560991
  40. Novel transcriptional control of the pyruvate formate-lyase gene: upstream regulatory sequences and multiple promoters regulate anaerobic expression.
    J Bacteriol. 1989 May;171(5):2485-98 PMID: 2651404
  41. Reconstruction of regulatory and metabolic pathways in metal-reducing delta-proteobacteria.
    Genome Biol. 2004;5(11):R90 PMID: 15535866
  42. The Iron control element, acting in positive and negative control of iron-regulated Bradyrhizobium japonicum genes, is a target for the Irr protein.
    J Bacteriol. 2006 Jan;188(2):733-44 PMID: 16385063
  43. Bacterial iron homeostasis.
    FEMS Microbiol Rev. 2003 Jun;27(2-3):215-37 PMID: 12829269
  44. The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.
    J Biol Chem. 1998 Aug 21;273(34):21669-74 PMID: 9705301
  45. Role of the regulatory gene rirA in the transcriptional response of Sinorhizobium meliloti to iron limitation.
    Appl Environ Microbiol. 2005 Oct;71(10):5969-82 PMID: 16204511
  46. Proteomic analysis reveals the wide-ranging effects of the novel, iron-responsive regulator RirA in Rhizobium leguminosarum bv. viciae.
    Mol Genet Genomics. 2005 Apr;273(2):197-206 PMID: 15856304
  47. Deletion of two downstream genes alters expression of the hmc operon of Desulfovibrio vulgaris subsp. vulgaris Hildenborough.
    Arch Microbiol. 1997 Jun;167(6):376-83 PMID: 9148780
  48. Oxygen control of the Bradyrhizobium japonicum hemA gene.
    J Bacteriol. 1995 Jul;177(14):3979-84 PMID: 7608070
  49. Promoters in the nodulation region of the Rhizobium leguminosarum Sym plasmid pRL1JI.
    Plant Mol Biol. 1987 Jan;9(1):27-39 PMID: 24276795
  50. BLAST: at the core of a powerful and diverse set of sequence analysis tools.
    Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W20-5 PMID: 15215342
  51. The nodD gene of Rhizobium leguminosarum is autoregulatory and in the presence of plant exudate induces the nodA,B,C genes.
    EMBO J. 1985 Dec 16;4(13A):3369-73 PMID: 16453650
  52. Expression of nitrite reductase in Nitrosomonas europaea involves NsrR, a novel nitrite-sensitive transcription repressor.
    Mol Microbiol. 2004 Oct;54(1):148-58 PMID: 15458412
  53. The Sinorhizobium meliloti fur gene regulates, with dependence on Mn(II), transcription of the sitABCD operon, encoding a metal-type transporter.
    J Bacteriol. 2004 Jun;186(11):3609-20 PMID: 15150249
  54. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.
    Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 PMID: 9396791
  55. Expression of the Rhodobacter sphaeroides hemA and hemT genes, encoding two 5-aminolevulinic acid synthase isozymes.
    J Bacteriol. 1993 Apr;175(8):2292-303 PMID: 8468290
Article Info
Journal
Molecular genetics and genomics : MGG
Abbr.
Mol Genet Genomics
ISSN
1617-4615
DOI
10.1007/s00438-006-0115-y
Published
2006-06-00
Epub
2006-00-20
Pages
564-77
Language
English
Region
Germany
NLM ID
101093320
Subset
IM
External Links
PubMed source DOI: 10.1007/s00438-006-0115-y View journal details
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