The cytolethal distending toxin of Haemophilus ducreyi aggravates dermal lesions in a rabbit model of chancroid

2005 ◽  
Vol 7 (5-6) ◽  
pp. 867-874 ◽  
Author(s):  
Catharina Wising ◽  
Lena Mölne ◽  
Ing-Marie Jonsson ◽  
Karin Ahlman ◽  
Teresa Lagergård
Keyword(s):  
Rabbit Model ◽  
Haemophilus Ducreyi ◽  
Cytolethal Distending Toxin ◽  
Dermal Lesions

A Temperature-Dependent Rabbit Model for Production of Dermal Lesions by Haemophilus ducreyi

1991 ◽  
Vol 164 (2) ◽  
pp. 359-367 ◽  
Author(s):  
B. K. Purcell ◽  
J. A. Richardson ◽  
J. D. Radolf ◽  
E. J. Hansen
Keyword(s):  
Rabbit Model ◽  
Haemophilus Ducreyi ◽  
Temperature Dependent ◽  
Dermal Lesions

Toxicity and immunogenicity of purified Haemophilus ducreyi cytolethal distending toxin in a rabbit model

2002 ◽  
Vol 33 (2) ◽  
pp. 49-62 ◽  
Author(s):  
Catharina Wising ◽  
Liselott A. Svensson ◽  
Hinda J. Ahmed ◽  
Vivianne Sundaeus ◽  
Karin Ahlman ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Haemophilus Ducreyi ◽  
Cytolethal Distending Toxin

scholarly journals Prevalence of cdtABC genes encoding cytolethal distending toxin among Haemophilus ducreyi and Actinobacillus actinomycetemcomitans strains

2001 ◽  
Vol 50 (10) ◽  
pp. 860-864 ◽  
Author(s):  
H.J. AHMED ◽  
L.A. SVENSSON ◽  
L.D. COPE ◽  
J.L. LATIMER ◽  
E.J. HANSEN ◽  
...  
Keyword(s):  
Actinobacillus Actinomycetemcomitans ◽  
Haemophilus Ducreyi ◽  
Cytolethal Distending Toxin ◽  
Genes Encoding

The impact of Haemophilus ducreyi cytolethal distending toxin on cells involved in immune response

2001 ◽  
Vol 30 (3) ◽  
pp. 157-166 ◽  
Author(s):  
Liselott A. Svensson ◽  
Andrzej Tarkowski ◽  
Monica Thelestam ◽  
Teresa Lagergård
Keyword(s):  
Immune Response ◽  
Haemophilus Ducreyi ◽  
Cytolethal Distending Toxin ◽  
The Impact

scholarly journals Expression of the cytolethal distending toxin in a geographically diverse collection of Haemophilus ducreyi clinical isolates

2003 ◽  
Vol 79 (4) ◽  
pp. 294-297 ◽  
Author(s):  
K Kulkarni ◽  
D A Lewis ◽  
C A Ison
Keyword(s):  
Haemophilus Ducreyi ◽  
Clinical Isolates ◽  
Cytolethal Distending Toxin

scholarly journals Cytolethal Distending Toxin of Haemophilus ducreyi Induces Apoptotic Death of Jurkat T Cells

1999 ◽  
Vol 67 (12) ◽  
pp. 6394-6402 ◽  
Author(s):  
Valentina Gelfanova ◽  
Eric J. Hansen ◽  
Stanley M. Spinola
Keyword(s):  
T Cells ◽  
T Cell ◽  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Haemophilus Ducreyi ◽  
Cytolethal Distending Toxin ◽  
Jurkat T Cells ◽  
Toxic Activity ◽  
Heat Labile ◽  
Human T Cell

ABSTRACT The immune response to Haemophilus ducreyi is mediated in part by T cells infiltrating the site of infection. In this study, we show that H. ducreyi antigen preparations inhibited the proliferation of peripheral blood mononuclear cells and primary human T-cell lines. H. ducreyi also inhibited Jurkat T-cell proliferation and induced apoptosis of Jurkat T cells, confirmed through the detection of DNA degradation and membrane unpacking. The cytotoxic product(s) was present in cell-free culture supernatant and whole-cell preparations of H. ducreyi and was heat labile.H. ducreyi produces two known heat-labile toxins, a hemolysin and a cytolethal distending toxin (CDT). Whole cells and supernatants prepared from a hemolysin-deficient mutant had the same inhibitory and apoptotic effects on Jurkat T cells as did its isogenic parent. Preparations made from an H. ducreyi cdtC mutant were less toxic and induced less apoptosis than the parent. The toxic activity of the cdtC mutant was restored by complementation in trans. CdtC-neutralizing antibodies also inhibitedH. ducreyi-induced toxicity and apoptosis. The data suggest that CDT may interfere with T-cell responses to H. ducreyiby induction of apoptosis.

Induction of apoptosis/necrosis in various human cell lineages by Haemophilus ducreyi cytolethal distending toxin

Toxicon ◽  
2005 ◽  
Vol 45 (6) ◽  
pp. 767-776 ◽  
Author(s):  
Catharina Wising ◽  
Jozef Azem ◽  
Madeleine Zetterberg ◽  
Liselott A. Svensson ◽  
Karin Ahlman ◽  
...  
Keyword(s):  
Human Cell ◽  
Haemophilus Ducreyi ◽  
Cytolethal Distending Toxin ◽  
Cell Lineages ◽  
Induction Of Apoptosis

scholarly journals Inhibition of Phagocytosis by Haemophilus ducreyi Requires Expression of the LspA1 and LspA2 Proteins

2003 ◽  
Vol 71 (10) ◽  
pp. 5994-6003 ◽  
Author(s):  
Merja Vakevainen ◽  
Steven Greenberg ◽  
Eric J. Hansen
Keyword(s):  
Type Strain ◽  
Wild Type Strain ◽  
Rabbit Model ◽  
Inhibitory Effect ◽  
Haemophilus Ducreyi ◽  
Bacterial Cells ◽  
Wild Type ◽  
Temperature Dependent ◽  
Live Bacterial Cells

ABSTRACT Haemophilus ducreyi previously has been shown to inhibit the phagocytosis of both secondary targets and itself by certain cells in vitro. Wild-type H. ducreyi strain 35000HP contains two genes, lspA1 and lspA2, whose encoded protein products are predicted to be 456 and 543 kDa, respectively. An isogenic mutant of H. ducreyi 35000HP with inactivated lspA1 and lspA2 genes has been shown to exhibit substantially decreased virulence in the temperature-dependent rabbit model for chancroid. This lspA1 lspA2 mutant was tested for its ability to inhibit phagocytosis of immunoglobulin G-opsonized particles by differentiated HL-60 and U-937 cells and by J774A.1 cells. The wild-type strain H. ducreyi 35000HP readily inhibited phagocytosis, whereas the lspA1 lspA2 mutant was unable to inhibit phagocytosis. Similarly, the wild-type strain was resistant to phagocytosis, whereas the lspA1 lspA2 mutant was readily engulfed by phagocytes. This inhibitory effect of wild-type H. ducreyi on phagocytic activity was primarily associated with live bacterial cells but could also be found, under certain conditions, in concentrated H. ducreyi culture supernatant fluids that lacked detectable outer membrane fragments. Both the wild-type strain and the lspA1 lspA2 mutant attached to phagocytes at similar levels. These results indicate that the LspA1 and LspA2 proteins of H. ducreyi are involved, directly or indirectly, in the antiphagocytic activity of this pathogen, and they provide a possible explanation for the greatly reduced virulence of the lspA1 lspA2 mutant.

scholarly journals Haemophilusducreyi Requires an Intact flp Gene Cluster for VirulenceinHumans

2003 ◽  
Vol 71 (12) ◽  
pp. 7178-7182 ◽  
Author(s):  
Stanley M. Spinola ◽  
Kate R. Fortney ◽  
Barry P. Katz ◽  
Jo L. Latimer ◽  
Jason R. Mock ◽  
...  
Keyword(s):  
Animal Model ◽  
Gene Cluster ◽  
Rabbit Model ◽  
Type Iv Secretion ◽  
Haemophilus Ducreyi ◽  
Secretion Systems ◽  
Temperature Dependent ◽  
Type Iv ◽  
Human Volunteers

ABSTRACT An intact Haemophilus ducreyi flp operon is essential for microcolony formation in vitro. tadA is the 9th of 15 genes in the operon and has homology to NTPases of type IV secretion systems. Fifteen human volunteers were experimentally infected with both H. ducreyi 35000HP and the tadA mutant, 35000HP.400. Papules developed at similar rates at sites inoculated with the mutant and parent, while pustules formed at 36.4% of parent sites and at 0% of mutant sites (P = 0.001). Compared to 35000HP, 35000HP.400 had only a modest but significant reduction in lesion scores in the temperature-dependent rabbit model of chancroid. These data suggest that proteins secreted by the flp locus are required for full expression of virulence by H. ducreyi in humans but have less of a role in virulence in an animal model of infection.

scholarly journals Characterization of a Haemophilus ducreyi Mutant Deficient in Expression of Cytolethal Distending Toxin

1999 ◽  
Vol 67 (8) ◽  
pp. 3900-3908 ◽  
Author(s):  
Marla K. Stevens ◽  
Jo L. Latimer ◽  
Sheryl R. Lumbley ◽  
Christine K. Ward ◽  
Leslie D. Cope ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Hela Cells ◽  
Culture Supernatant ◽  
Haemophilus Ducreyi ◽  
Cytolethal Distending Toxin ◽  
Supernatant Fluid ◽  
Hacat Keratinocytes ◽  
Wild Type ◽  
Insertional Inactivation

ABSTRACT Haemophilus ducreyi expresses a soluble cytolethal distending toxin (CDT) that kills HeLa, HEp-2, and other human epithelial cells in vitro. H. ducreyi CDT activity is encoded by a three-gene cluster (cdtABC), and antibody to the cdtC gene product can neutralize CDT activity in vitro (L. D. Cope, S. R. Lumbley, J. L. Latimer, J. Klesney-Tait, M. K. Stevens, L. S. Johnson, M. Purven, R. S. Munson, Jr., T. Lagergard, J. D. Radolf, and E. J. Hansen, Proc. Natl. Acad. Sci. USA 94:4056–4061, 1997). Culture supernatant fluid from a recombinant Escherichia colistrain containing the H. ducreyi cdtABC gene cluster readily killed both HeLa cells and HaCaT keratinocytes and had a modest inhibitory effect on the growth of human foreskin fibroblasts. Insertional inactivation of the cdtC gene in this recombinant E. coli strain eliminated the ability of this strain to kill HeLa cells and HaCaT keratinocytes. This mutatedH. ducreyi cdtABC gene cluster was used to construct an isogenic H. ducreyi cdtC mutant. Monoclonal antibodies against the H. ducreyi CdtA, CdtB, and CdtC proteins were used to characterize protein expression by this cdtCmutant. Culture supernatant fluid from this H. ducreyi cdtCmutant did not detectably affect any of the human cells used in this study. The presence of the wild-type H. ducreyi cdtC gene in trans in this H. ducreyi mutant restored its ability to express a CDT that killed both HeLa cells and HaCaT keratinocytes. The isogenic H. ducreyi cdtC mutant was shown to be as virulent as its wild-type parent strain in the temperature-dependent rabbit model for experimental chancroid. Lack of expression of the H. ducreyi CdtC protein also did not affect the ability of this H. ducreyi mutant to survive in the skin of rabbits.

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