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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,dagger 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 Delta 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 Delta 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.

dagger 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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