Expression of sialylated or paragloboside-like lipooligosaccharides are not required for pustule formation by Haemophilus ducreyi in human volunteers

Royden S. Young, Kate Fortney, Jennifer C. Haley, Antoinette F. Hood, Anthony A. Campagnari, Jing Wang, Joel A. Bozue, Robert S. Munson, Stanley Spinola

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The lipooligosaccharide (LOS) of Haemophilus ducreyi, the etiologic agent of chancroid, chemically and immunologically resembles human glycosphingolipid antigens. To test whether LOS that contains paragloboside- like structures was required for pustule formation, an isogenic mutant (35000HP-RSM2) was constructed in losB, which encodes D-glycero-D-manno- heptosyltransferase. 35000HP-RSM2 produces a truncated LOS whose major glycoform terminates in a single glucose attached to a heptose trisaccharide core and 2-keto-3-deoxyoctulosonic acid. Five human subjects were inoculated with 35000HP and 35000HP-RSM2 in a dose response trial. For estimated delivered doses (EDDs) of ≥25 CFU, the pustule formation rates were 80% for 35000HP and 58% for 35000HP-RSM2. Preliminary data indicated that a previously described Tn916 losB mutant made a minor glycoform that does not require DD-heptose to form the terminal N-acetyllactosamine. If 35000HP-RSM2 made this glycoform, then 35000HP-RSM2 could theoretically make a sialylated glycoform. To test whether sialylated LOS was required for pustule formation, a second trial comparing an isogenic sialyltransferase mutant (35000HP- RSM203) to 35000HP was performed in five additional subjects. For EDDs of ≥25 CFU, the pustule formation rates were 30% for both 35000HP and 35000HP- RSM203. The histopathology and recovery rates of H. ducreyi from surface cultures and biopsies obtained from mutant and parent sites in both trials were similar. These results indicate that neither the expression of a major glycoform resembling paragloboside nor sialylated LOS is required for pustule formation by H. ducreyi in humans.

Original languageEnglish
Pages (from-to)6335-6340
Number of pages6
JournalInfection and Immunity
Volume67
Issue number12
StatePublished - Dec 1999

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Haemophilus ducreyi
Volunteers
Heptoses
Chancroid
Sialyltransferases
Trisaccharides
Glycosphingolipids
lipid-linked oligosaccharides
paragloboside
Biopsy
Antigens
Glucose

ASJC Scopus subject areas

  • Immunology

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Expression of sialylated or paragloboside-like lipooligosaccharides are not required for pustule formation by Haemophilus ducreyi in human volunteers. / Young, Royden S.; Fortney, Kate; Haley, Jennifer C.; Hood, Antoinette F.; Campagnari, Anthony A.; Wang, Jing; Bozue, Joel A.; Munson, Robert S.; Spinola, Stanley.

In: Infection and Immunity, Vol. 67, No. 12, 12.1999, p. 6335-6340.

Research output: Contribution to journalArticle

Young, RS, Fortney, K, Haley, JC, Hood, AF, Campagnari, AA, Wang, J, Bozue, JA, Munson, RS & Spinola, S 1999, 'Expression of sialylated or paragloboside-like lipooligosaccharides are not required for pustule formation by Haemophilus ducreyi in human volunteers', Infection and Immunity, vol. 67, no. 12, pp. 6335-6340.
Young, Royden S. ; Fortney, Kate ; Haley, Jennifer C. ; Hood, Antoinette F. ; Campagnari, Anthony A. ; Wang, Jing ; Bozue, Joel A. ; Munson, Robert S. ; Spinola, Stanley. / Expression of sialylated or paragloboside-like lipooligosaccharides are not required for pustule formation by Haemophilus ducreyi in human volunteers. In: Infection and Immunity. 1999 ; Vol. 67, No. 12. pp. 6335-6340.
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abstract = "The lipooligosaccharide (LOS) of Haemophilus ducreyi, the etiologic agent of chancroid, chemically and immunologically resembles human glycosphingolipid antigens. To test whether LOS that contains paragloboside- like structures was required for pustule formation, an isogenic mutant (35000HP-RSM2) was constructed in losB, which encodes D-glycero-D-manno- heptosyltransferase. 35000HP-RSM2 produces a truncated LOS whose major glycoform terminates in a single glucose attached to a heptose trisaccharide core and 2-keto-3-deoxyoctulosonic acid. Five human subjects were inoculated with 35000HP and 35000HP-RSM2 in a dose response trial. For estimated delivered doses (EDDs) of ≥25 CFU, the pustule formation rates were 80{\%} for 35000HP and 58{\%} for 35000HP-RSM2. Preliminary data indicated that a previously described Tn916 losB mutant made a minor glycoform that does not require DD-heptose to form the terminal N-acetyllactosamine. If 35000HP-RSM2 made this glycoform, then 35000HP-RSM2 could theoretically make a sialylated glycoform. To test whether sialylated LOS was required for pustule formation, a second trial comparing an isogenic sialyltransferase mutant (35000HP- RSM203) to 35000HP was performed in five additional subjects. For EDDs of ≥25 CFU, the pustule formation rates were 30{\%} for both 35000HP and 35000HP- RSM203. The histopathology and recovery rates of H. ducreyi from surface cultures and biopsies obtained from mutant and parent sites in both trials were similar. These results indicate that neither the expression of a major glycoform resembling paragloboside nor sialylated LOS is required for pustule formation by H. ducreyi in humans.",
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AU - Young, Royden S.

AU - Fortney, Kate

AU - Haley, Jennifer C.

AU - Hood, Antoinette F.

AU - Campagnari, Anthony A.

AU - Wang, Jing

AU - Bozue, Joel A.

AU - Munson, Robert S.

AU - Spinola, Stanley

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