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Journal of Bacteriology, June 1999, p. 3402-3408, Vol. 181, No. 11
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Transcriptional Control of the Iron-Responsive
fxbA Gene by the Mycobacterial Regulator
IdeR
Olivier
Dussurget,1,2
Juliano
Timm,1
Manuel
Gomez,1
Benjamin
Gold,1,3
Shengwei
Yu,4
Sue Z.
Sabol,5
Randall K.
Holmes,6
William R.
Jacobs Jr.,4 and
Issar
Smith1,*
TB Center, Public Health Research
Institute,1 and Department of
Microbiology, New York University Medical
Center,3 New York, New York 10016; UFR
de Biochimie, Université Paris 7, 75251 Paris Cedex 05, France2; Department of Microbiology and
Immunology, Howard Hughes Medical Institute, Albert Einstein College of
Medicine, Bronx, New York 104614;
Section of Gene Structure and Regulation, Laboratory of
Biochemistry, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland 208925; and
Department of Microbiology, University of Colorado Health
Sciences Center, Denver, Colorado 802626
Received 12 March 1998/Accepted 30 March 1999
Exochelin is the primary extracellular siderophore of
Mycobacterium smegmatis, and the iron-regulated
fxbA gene encodes a putative formyltransferase, an
essential enzyme in the exochelin biosynthetic pathway (E. H. Fiss, Y. Yu, and W. R. Jacobs, Jr., Mol. Microbiol. 14:557-569,
1994). We investigated the regulation of fxbA by the
mycobacterial IdeR, a homolog of the Corynebacterium diphtheriae iron regulator DtxR (M. P. Schmitt, M. Predich,
L. Doukhan, I. Smith, and R. K. Holmes, Infect. Immun.
63:4284-4289, 1995). Gel mobility shift experiments showed that IdeR
binds to the fxbA regulatory region in the presence of
divalent metals. DNase I footprinting assays indicated that IdeR
binding protects a 28-bp region containing a palindromic sequence of
the fxbA promoter that was identified in primer extension
assays. fxbA regulation was measured in M. smegmatis wild-type and ideR mutant strains containing fxbA promoter-lacZ fusions. These
experiments confirmed that fxbA expression is negatively
regulated by iron and showed that inactivation of ideR
results in iron-independent expression of fxbA. However,
the levels of its expression in the ideR mutant were
approximately 50% lower than those in the wild-type strain under iron
limitation, indicating an undefined positive role of IdeR in the
regulation of fxbA.
*
Corresponding author. Mailing address: TB Center,
Public Health Research Institute, 455 First Ave., New York, NY 10016. Phone: (212) 578-0867. Fax: (212) 578-0804. E-mail:
smitty{at}phri.nyu.edu.
Publication no. 64 from the TB Center, Public Health Research Institute.
Journal of Bacteriology, June 1999, p. 3402-3408, Vol. 181, No. 11
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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