title: Antiparallel and interlinked control of cellular iron levels by the Irr and RirA regulators of Agrobacterium tumefaciens.
abstract: The plant pathogen Agrobacterium tumefaciens encodes predicted iron-responsive regulators, Irr and RirA, that function in several other bacteria to control the response to environmental iron levels. Deletion mutations of irr and rirA, alone and in combination, were evaluated for their impact on cellular iron response. Growth was severely diminished in the Δirr mutant under iron-limiting conditions, but reversed to wild-type levels in an Δirr ΔrirA mutant. The level of uncomplexed iron in the Δirr mutant was decreased, whereas the ΔrirA mutant exhibited elevated iron levels. Sensitivity of the Δirr and ΔrirA mutants to iron-activated antimicrobial compounds generally reflected their uncomplexed-iron levels. Expression of genes that encode iron uptake systems was decreased in the Δirr mutant, whereas that of iron utilization genes was increased. Irr function required a trihistidine repeat likely to mediate interactions with heme. Iron uptake genes were derepressed in the ΔrirA mutant. In the Δirr ΔrirA mutant, iron uptake and utilization genes were derepressed, roughly combining the phenotypes of the single mutants. Siderophore production was elevated in the rirA mutant, but most strongly regulated by an RirA-controlled sigma factor. Expression of rirA itself was regulated by Irr, RirA, and iron availability, in contrast to irr expression, which was relatively stable in the different mutants. These studies suggest that in A. tumefaciens, the Irr protein is most active under low-iron conditions, inhibiting iron utilization and activating iron acquisition, while the RirA protein is active under high-iron conditions, repressing iron uptake.
authors: Department of Biology, Indiana University, Bloomington, IN 47405-1847, USA.
authors: Michael E
authors: ME
authors: Hibbing
authors: Clay
authors: C
authors: Fuqua
references: Microbiology (Reading). 2004 Dec;150(Pt 12):4065-74
references: 15583159
references: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W299-307
references: 20542910
references: J Bacteriol. 1995 May;177(9):2305-14
references: 7730258
references: J Biol Chem. 1981 Jul 25;256(14):7094-6
references: 6265438
references: FEMS Microbiol Rev. 2006 Jul;30(4):631-48
references: 16774589
references: Appl Environ Microbiol. 2007 Aug;73(15):4832-8
references: 17557847
references: Microbiology (Reading). 2002 Dec;148(Pt 12):4059-4071
references: 12480909
references: J Bacteriol. 2007 Nov;189(22):8005-14
references: 17766409
references: Microbiology (Reading). 2004 May;150(Pt 5):1447-1456
references: 15133106
references: Appl Environ Microbiol. 2008 Aug;74(16):5053-62
references: 18606801
references: Biochem Biophys Res Commun. 1982 May 31;106(2):407-11
references: 7049174
references: J Bacteriol. 2004 Jul;186(14):4492-501
references: 15231781
references: Mol Gen Genet. 1981;182(2):288-92
references: 7026976
references: Infect Immun. 2009 Aug;77(8):3466-74
references: 19487482
references: Microbiology (Reading). 2006 Sep;152(Pt 9):2591-2598
references: 16946254
references: Mol Microbiol. 2006 Apr;60(2):427-37
references: 16573691
references: Microbiology (Reading). 2002 Aug;148(Pt 8):2273-2282
references: 12177321
references: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14895-900
references: 11742080
references: Mol Cell. 2002 Jan;9(1):155-62
references: 11804594
references: J Biol Chem. 1995 Nov 10;270(45):26723-6
references: 7592901
references: Trends Biochem Sci. 1999 Mar;24(3):104-9
references: 10203757
references: Biometals. 2007 Jun;20(3-4):501-11
references: 17310401
references: Science. 1988 Jun 3;240(4857):1302-9
references: 3287616
references: J Biol Chem. 2010 May 21;285(21):16023-31
references: 20233710
references: Proc Natl Acad Sci U S A. 1977 Jul;74(7):2848-9
references: 16592419
references: Mol Genet Genomics. 2006 Jun;275(6):564-77
references: 16625355
references: Science. 2001 Dec 14;294(5550):2317-23
references: 11743193
references: Microbiology (Reading). 2004 Nov;150(Pt 11):3857-3866
references: 15528670
references: J Biol Chem. 2005 Mar 4;280(9):7671-6
references: 15613477
references: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9542-7
references: 12883001
references: Microbiology (Reading). 2005 Oct;151(Pt 10):3427-3433
references: 16207924
references: Proc Natl Acad Sci U S A. 1980 Dec;77(12):6973-7
references: 16592930
references: Biochemistry. 2006 Feb 28;45(8):2686-98
references: 16489762
references: Mol Microbiol. 2002 Sep;45(5):1177-90
references: 12207687
references: Gene. 1990 May 31;90(1):149-51
references: 2165971
references: Science. 1988 Apr 29;240(4852):640-2
references: 2834821
references: Science. 2001 Dec 14;294(5550):2323-8
references: 11743194
references: Nat Rev Microbiol. 2010 Jan;8(1):15-25
references: 19946288
references: Mol Microbiol. 2009 Dec;74(5):1257-71
references: 19889096
references: Gene. 1997 Feb 20;186(1):29-35
references: 9047341
references: J Biol Chem. 1999 Jan 8;274(2):962-71
references: 9873038
references: J Biol Chem. 1987 Oct 5;262(28):13404-8
references: 2820968
references: Methods Enzymol. 1994;235:329-44
references: 8057905
references: FEMS Microbiol Lett. 2003 Aug 8;225(1):167-72
references: 12900037
references: Biometals. 2009 Feb;22(1):89-97
references: 19093075
references: J Bacteriol. 2009 Apr;191(7):2083-90
references: 19168612
references: Anal Biochem. 1987 Jan;160(1):47-56
references: 2952030
references: Genome Res. 2004 Jun;14(6):1188-90
references: 15173120
references: Biometals. 2000 Jun;13(2):165-8
references: 11016405
references: Mol Genet Genomics. 2005 Apr;273(2):197-206
references: 15856304
references: J Bacteriol. 2006 Jan;188(2):733-44
references: 16385063
references: Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13056-61
references: 10557272
references: FEMS Microbiol Rev. 2003 Jun;27(2-3):215-37
references: 12829269
references: ISME J. 2008 Jan;2(1):49-55
references: 18180746
references: J Biol Chem. 1998 Aug 21;273(34):21669-74
references: 9705301
references: Mol Microbiol. 1998 Jun;28(5):961-70
references: 9663682
references: Nat Rev Mol Cell Biol. 2003 Feb;4(2):105-16
references: 12563288
references: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9722-7
references: 15210995
references: Mol Microbiol. 2003 Feb;47(4):903-15
references: 12581348
references: Trends Plant Sci. 2003 Aug;8(8):380-6
references: 12927971
references: Mol Microbiol. 2001 Aug;41(4):787-800
references: 11532144
references: Biometals. 2007 Jun;20(3-4):485-99
references: 17216355
references: PLoS Comput Biol. 2006 Dec 15;2(12):e163
references: 17173478
references: Appl Environ Microbiol. 2007 Aug;73(15):4760-8
references: 17545320
references: Biochem Pharmacol. 1994 Oct 7;48(7):1427-35
references: 7945443
references: J Biol Chem. 2002 Feb 22;277(8):5866-74
references: 11717314
references: Can J Biochem. 1976 Mar;54(3):219-23
references: 1260505
references: Mol Microbiol. 2006 May;60(4):1058-75
references: 16677314
references: Mol Microbiol. 2002 Sep;45(6):1613-29
references: 12354229
references: Mol Microbiol. 2006 Nov;62(4):1181-90
references: 17078818