A superoxide dismutase C mutant of Haemophilus ducreyi is virulent in human volunteers

Cliffton T H Bong, Kate R. Fortney, Barry Katz, Antoinette F. Hood, Lani R. San Mateo, Thomas H. Kawula, Stanley Spinola

Research output: Contribution to journalArticle

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Abstract

Haemophilus ducreyi produces a periplasmic copper-zinc superoxide dismutase (Cu-Zn SOD), which is thought to protect the organism from exogenous reactive oxygen species generated by neutrophils during an inflammatory response. We had previously identified the gene, sodC, responsible for the production and secretion of Cu-Zn SOD and constructed an isogenic H. ducreyi strain with a mutation in the sodC gene (35000HP-sodC-cat). Compared to the parent, the mutant does not survive in the presence of exogenous superoxide (L. R. San Mateo, M. Hobbs, and T. H. Kawula, Mol. Microbiol. 27:391-404, 1998) and is impaired in the swine model of H. ducreyi infection (L. R. San Mateo, K. L. Toffer, P. E. Orndorff, and T. H. Kawula, Infect. Immun. 67:5345-5351, 1999). To test whether Cu-Zn SOD is important for bacterial survival in vivo, six human volunteers were experimentally infected with 35000HP and 35000HP-sodC-cat and observed for papule and pustule formation. Papules developed at similar rates at sites inoculated with the mutant or parent. The pustule formation rates were 75% (95% confidence intervals [CI], 43 to 95%) at 12 parent-inoculated sites and 67% (95% CI, 41 to 88%) at 18 mutant-inoculated sites (P = 0.47). There was no significant difference in levels of H. ducreyi recovery from mutant- and parent-inoculated biopsy sites. These results suggest that expression of Cu-Zn SOD does not play a major role in the survival of this pathogen in the initial stages of experimental infection of humans.

Original languageEnglish
Pages (from-to)1367-1371
Number of pages5
JournalInfection and Immunity
Volume70
Issue number3
DOIs
StatePublished - 2002

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Haemophilus ducreyi
Superoxide Dismutase
Volunteers
Cats
Haemophilus Infections
Confidence Intervals
Survival
Superoxides
Genes
Zinc
Copper
Reactive Oxygen Species
Neutrophils
Swine
Biopsy
Mutation
Infection

ASJC Scopus subject areas

  • Immunology

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A superoxide dismutase C mutant of Haemophilus ducreyi is virulent in human volunteers. / Bong, Cliffton T H; Fortney, Kate R.; Katz, Barry; Hood, Antoinette F.; San Mateo, Lani R.; Kawula, Thomas H.; Spinola, Stanley.

In: Infection and Immunity, Vol. 70, No. 3, 2002, p. 1367-1371.

Research output: Contribution to journalArticle

Bong, Cliffton T H ; Fortney, Kate R. ; Katz, Barry ; Hood, Antoinette F. ; San Mateo, Lani R. ; Kawula, Thomas H. ; Spinola, Stanley. / A superoxide dismutase C mutant of Haemophilus ducreyi is virulent in human volunteers. In: Infection and Immunity. 2002 ; Vol. 70, No. 3. pp. 1367-1371.
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abstract = "Haemophilus ducreyi produces a periplasmic copper-zinc superoxide dismutase (Cu-Zn SOD), which is thought to protect the organism from exogenous reactive oxygen species generated by neutrophils during an inflammatory response. We had previously identified the gene, sodC, responsible for the production and secretion of Cu-Zn SOD and constructed an isogenic H. ducreyi strain with a mutation in the sodC gene (35000HP-sodC-cat). Compared to the parent, the mutant does not survive in the presence of exogenous superoxide (L. R. San Mateo, M. Hobbs, and T. H. Kawula, Mol. Microbiol. 27:391-404, 1998) and is impaired in the swine model of H. ducreyi infection (L. R. San Mateo, K. L. Toffer, P. E. Orndorff, and T. H. Kawula, Infect. Immun. 67:5345-5351, 1999). To test whether Cu-Zn SOD is important for bacterial survival in vivo, six human volunteers were experimentally infected with 35000HP and 35000HP-sodC-cat and observed for papule and pustule formation. Papules developed at similar rates at sites inoculated with the mutant or parent. The pustule formation rates were 75{\%} (95{\%} confidence intervals [CI], 43 to 95{\%}) at 12 parent-inoculated sites and 67{\%} (95{\%} CI, 41 to 88{\%}) at 18 mutant-inoculated sites (P = 0.47). There was no significant difference in levels of H. ducreyi recovery from mutant- and parent-inoculated biopsy sites. These results suggest that expression of Cu-Zn SOD does not play a major role in the survival of this pathogen in the initial stages of experimental infection of humans.",
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