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Infection and Immunity, March 2000, p. 1608-1619, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Serum Resistance in Haemophilus ducreyi
Requires Outer Membrane Protein DsrA
Christopher
Elkins,1,2,*
K. John
Morrow Jr.,3 and
Bonnie
Olsen1
Departments of
Medicine1 and Microbiology and
Immunology,2 School of Medicine, University of
North Carolina, Chapel Hill, North Carolina 27599, and
Department of Cell Biology and Biochemistry, Texas Tech
Health Science Center, Lubbock, Texas 794303
Received 22 September 1999/Returned for modification 3 November
1999/Accepted 12 December 1999
Haemophilus ducreyi is resistant to killing by normal
serum antibody and complement. We discovered an H. ducreyi
outer membrane protein required for expression of serum resistance and
termed it DsrA (for "ducreyi serum resistance A"). The
dsrA locus was cloned, sequenced, and mutagenized. An
isogenic mutant (FX517) of parent strain 35000 was constructed and
characterized, and it was found to no longer express dsrA.
FX517 was at least 10-fold more serum susceptible than 35000. DsrA was
expressed by all strains of H. ducreyi tested, except three
naturally occurring, avirulent, serum-sensitive strains. FX517 and the
three naturally occurring dsrA-nonexpressing strains were
complemented in trans with a plasmid expressing
dsrA. All four strains were converted to a serum-resistant phenotype, including two that contained truncated lipooligosaccharide (LOS). Therefore, serum resistance in H. ducreyi does not
require expression of full-length LOS but does require expression of
dsrA. The dsrA locus from eight additional
H. ducreyi strains was sequenced, and the deduced amino
acid sequences were more than 85% identical. The major difference
between the DsrA proteins was due to the presence of one, two, or three
copies of the heptameric amino acid repeat NTHNINK. These repeats
account for the variability in apparent molecular mass of the monomeric
form of DsrA (28 to 35 kDa) observed in sodium dodecyl
sulfate-polyacrylamide gel electrophoresis. Since DsrA is present in
virulent strains, is highly conserved, and is required for serum
resistance, we speculate that it may be a virulence factor and a
potential vaccine candidate.
*
Corresponding author. Mailing address: Departments of
Medicine and of Microbiology and Immunology, School of Medicine, Room 521 Burnett-Womack, Campus Box 7030, University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 966-3661. Fax: (919) 966-6714. E-mail: chriselk{at}med.unc.edu.
Infection and Immunity, March 2000, p. 1608-1619, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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