Haemophilus ducreyi is the causative agent of charoid, a sexually transmitted genital ulcerative disease. Chancroid is common in the developing world and occurs sporadically in North America. IN addition to the morbidity due to chancroid, genital ulcers are thought to facilitate the heterosexual transmission of HIV. The molecular mechanism(s) responsible for the formation of the chancroid ulcer are not known. The available data indicate that the lipoolgosaccaride (LOS) produced by H. ducreyi is an important virulence determinant. The principles investigator will characterize genes and gene products involved in the biosynthesis of H. ducreyi LOS and construct a series of isogenic strains that differ in the structure of their LOS. These strains will be tested in vitro models and in experimental human challenge studies in order to assess the role of the LOS in virulence and ulcer formation. These experiments will provide detailed information on the role of the LOS in pathogenesis, and structural requirements of the LOS which are critical for virulence. The data obtained in these studies will be pivotal to understanding the pathogenesis of chancroid and will provide insight into strategies for the prevention of this disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI038444-04
Application #
6124398
Study Section
Special Emphasis Panel (ZRG5-BM-2 (02))
Program Officer
Quackenbush, Robert L
Project Start
1996-12-15
Project End
2001-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
4
Fiscal Year
2000
Total Cost
$239,433
Indirect Cost
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
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Filiatrault, M J; Gibson, B W; Schilling, B et al. (2000) Construction and characterization of Haemophilus ducreyi lipooligosaccharide (LOS) mutants defective in expression of heptosyltransferase III and beta1,4-glucosyltransferase: identification of LOS glycoforms containing lactosamine repeats. Infect Immun 68:3352-61
Sun, S; Schilling, B; Tarantino, L et al. (2000) Cloning and characterization of the lipooligosaccharide galactosyltransferase II gene of Haemophilus ducreyi. J Bacteriol 182:2292-8
Bozue, J A; Tullius, M V; Wang, J et al. (1999) Haemophilus ducreyi produces a novel sialyltransferase. Identification of the sialyltransferase gene and construction of mutants deficient in the production of the sialic acid-containing glycoform of the lipooligosaccharide. J Biol Chem 274:4106-14

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