title: Brucella abortus requires the heme transporter BhuA for maintenance of chronic infection in BALB/c mice.
abstract: The gene annotated BAB2_1150 in the Brucella abortus 2308 genome sequence is predicted to encode a homolog of the well-characterized heme transporter ShuA of Shigella dysenteriae and accordingly has been given the designation bhuA (Brucella heme utilization). Phenotypic analysis of an isogenic bhuA mutant derived from B. abortus 2308 verified that there is a link between BhuA and the ability of the parent strain to use heme as an iron source in in vitro assays. Maximum expression of bhuA in B. abortus 2308 is observed during stationary phase when this strain in cultivated in low-iron minimal medium, and a comparison of the growth characteristics of the B. abortus bhuA mutant and 2308 in this medium suggested that heme serves as an important iron source for the parent strain during stationary phase. The B. abortus bhuA mutant HR1703 exhibits significant attenuation in cultured murine macrophages compared to strain 2308, and unlike its parent strain, the B. abortus bhuA mutant is unable to maintain a chronic spleen infection in experimentally infected BALB/c mice. These experimental findings suggest that heme and/or heme-containing proteins represent important iron sources for B. abortus 2308 during its residence in the mammalian host and that BhuA is required for efficient utilization of these iron sources.
authors: Department of Microbiology and Immunology, East Carolina University School of Medicine, 600 Moye Boulevard, Greenville, NC 27834, USA.
authors: James T
authors: JT
authors: Paulley
authors: Eric S
authors: ES
authors: Anderson
authors: R Martin
authors: RM
authors: Roop
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002003:Brucella abortus / Q000235:genetics / Q000472:pathogenicity*; D002006:Brucellosis / Q000382:microbiology*; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D005260:Female; D017353:Gene Deletion; D006418:Heme / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional; D013154:Spleen / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C524541:BhuA protein, Brucella abortus; D026901:Membrane Transport Proteins; D037521:Virulence Factors; D006418:Heme; D007501:Iron
references: Mol Microbiol. 2000 Feb;35(3):577-88
references: 10672180
references: Nat Rev Microbiol. 2004 Dec;2(12):946-53
references: 15550940
references: J Bacteriol. 2001 Apr;183(8):2454-62
references: 11274104
references: J Bacteriol. 2001 May;183(9):2715-23
references: 11292789
references: Mol Microbiol. 2001 Aug;41(4):787-800
references: 11532144
references: Infect Immun. 2001 Oct;69(10):6179-85
references: 11553558
references: Infect Immun. 2001 Oct;69(10):6225-30
references: 11553564
references: Mol Microbiol. 2001 Nov;42(3):835-49
references: 11722746
references: Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):443-8
references: 11756688
references: Tohoku J Exp Med. 2005 Apr;205(4):297-318
references: 15750326
references: J Bacteriol. 2005 Apr;187(8):2715-26
references: 15805518
references: Infect Immun. 2005 May;73(5):2873-80
references: 15845493
references: Infect Immun. 2005 Dec;73(12):8353-61
references: 16299333
references: Infect Immun. 2006 Nov;74(11):6213-25
references: 16966415
references: J Bacteriol. 2006 Dec;188(24):8421-9
references: 17041042
references: Microbiology. 2002 Feb;148(Pt 2):353-60
references: 11832499
references: Microb Pathog. 2002 May;32(5):239-48
references: 12071680
references: J Inorg Biochem. 2002 Jul 25;91(1):9-18
references: 12121757
references: Infect Immun. 2002 Oct;70(10):5390-403
references: 12228263
references: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13148-53
references: 12271122
references: Nucleic Acids Res. 2001 May 1;29(9):e45
references: 11328886
references: Infect Immun. 2003 Apr;71(4):1794-803
references: 12654793
references: Annu Rev Microbiol. 2003;57:57-76
references: 12730323
references: Mol Microbiol. 2004 May;52(3):621-30
references: 15101970
references: Infect Immun. 2004 Oct;72(10):5783-90
references: 15385478
references: J Biol Chem. 1986 Aug 15;261(23):10797-801
references: 3015941
references: J Bacteriol. 1991 Jan;173(2):417-25
references: 1898928
references: Mol Biol Cell. 1992 Aug;3(8):913-26
references: 1392079
references: Infect Immun. 1992 Nov;60(11):4496-503
references: 1398964
references: EMBO J. 1992 Dec;11(12):4359-67
references: 1425573
references: Infect Immun. 1994 Oct;62(10):4135-9
references: 7927667
references: J Bacteriol. 1994 Nov;176(21):6688-96
references: 7961422
references: Infect Immun. 1997 Dec;65(12):5358-63
references: 9393841
references: Biochimie. 1998 Feb;80(2):173-95
references: 9587675
references: Infect Immun. 1998 Jul;66(7):3134-41
references: 9632577
references: Mol Microbiol. 1998 Jun;28(6):1139-52
references: 9680204
references: Infect Immun. 1999 May;67(5):2615-8
references: 10225929
references: Infect Immun. 1999 Aug;67(8):3879-92
references: 10417152
references: J Bacteriol. 1999 Oct;181(19):6063-72
references: 10498719
references: Infect Immun. 2000 Nov;68(11):6329-36
references: 11035742