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Infection and Immunity, September 1998, p. 4254-4262, Vol. 66, No. 9
Departments of
Medicine1 and
Microbiology and
Immunology,2 School of Medicine, University
of North Carolina, Chapel Hill, North Carolina 27599
Received 6 April 1998/Returned for modification 5 May 1998/Accepted 24 June 1998
Haemophilus ducreyi is unable to synthesize heme and
must acquire it from its only known host, humans. We cloned and
sequenced a gene encoding an outer membrane receptor for heme. It was
designated tdhA (for TonB-dependent heme receptor A)
since it was related by sequence homology to the family of
TonB-dependent receptors. TdhA was strikingly similar to open reading
frame HI0113 from the genome of Haemophilus influenzae Rd
and also shared homology with five other heme receptors, including
HxuC, HemR, HmuR, ChuA, and ShuA, from gram-negative bacteria. An
Escherichia coli hemA tonB mutant strongly expressing
H. ducreyi tdhA grew on low levels of heme as a source of
heme only when an intact H. ducreyi Ton system plasmid was
present, formally demonstrating functional TonB dependence.
tdhA was expressed poorly in vitro by H. ducreyi and only under conditions of heme limitation. A survey of
H. ducreyi revealed that all tested strains but one
synthesized small amounts of TdhA in vitro under heme-limiting
conditions. Surprisingly, an isogenic mutant of tdhA as
well as its parent, 35000, both required the same high levels of heme
for growth (50 µg/ml [77 µM] on agar medium). This result,
together with previous findings, suggests that in vitro, the uptake of
heme by H. ducreyi is mediated by a TonB- and
TdhA-independent mechanism, possibly diffusion.
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Cloning and Characterization of tdhA, a
Locus Encoding a TonB-Dependent Heme Receptor from
Haemophilus ducreyi
*
Corresponding author. Mailing address: Department of
Medicine, CB 7030, School of Medicine, University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 966-3661. Fax: (919) 966-6714. E-mail: chriselk{at}med.unc.edu.
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