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Infection and Immunity, August 1999, p. 3879-3892, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Molecular Characterization of the Hemin Uptake Locus
(hmu) from Yersinia pestis and Analysis of
hmu Mutants for Hemin and Hemoprotein
Utilization
Jan M.
Thompson,
Heather A.
Jones, and
Robert D.
Perry*
Department of Microbiology and Immunology,
University of Kentucky, Lexington, Kentucky 40536-0084
Received 16 March 1999/Returned for modification 4 May
1999/Accepted 23 May 1999
Sequence analysis of the hemin uptake locus (hmu) of
Yersinia pestis revealed five genes, hmuRSTUV,
required for use of hemin and hemoproteins as iron sources. The
translated gene products have homologies with proteins of the hemin
transport genes of several gram-negative bacteria. Promoters were
identified upstream of hmuP'R (p1) and upstream of
hmuS (p2); p1, which contains a Fur box, is regulated by
iron and Fur, while p2 exhibits weak, but constitutive, activity. HmuR,
which has homology with TonB-dependent outer membrane (OM) receptors,
is localized to the OM of Y. pestis and is required for
utilizing hemin and all hemoproteins under iron-depleted conditions.
The proposed ABC transporter, HmuTUV, is necessary for use of hemin,
hemin-albumin, and myoglobin, but not hemoglobin,
hemoglobin-haptoglobin, or heme-hemopexin, as iron sources. In the
absence of HmuTUV, HmuS, a cytoplasmic protein, is involved in use of
hemoglobin and heme-hemopexin. In mice, the 50% lethal doses of
Y. pestis
hmuP'RSTUV mutants injected subcutaneously or retro-orbitally did not differ from that of the
Hmu+ parent strain. Thus, the hmu system is not
essential for infection in mice via these routes. Growth studies showed
that a
hmuP'RSTUV mutant could grow in iron-depleted
medium containing high concentrations of hemoglobin, suggesting that an
Hmu-independent, lower-affinity hemoglobin uptake system may exist.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, University of Kentucky, Lexington, KY
40536-0084. Phone: (606) 323-6341. Fax: (606) 257-8994. E-mail:
rperry{at}pop.uky.edu.

Née Jan M.
Hornung.
Infection and Immunity, August 1999, p. 3879-3892, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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