scholarly journals Acid‐Mediated Dissociation of Haemophilus ducreyi Cytolethal Distending Toxin Subunits Upon Cell Entry

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Isabel Silva ◽  
Carla Reyes ◽  
Ashley Fragoso ◽  
G. Robb Huhn ◽  
Ken Teter

2001 ◽  
Vol 50 (10) ◽  
pp. 860-864 ◽  
Author(s):  
H.J. AHMED ◽  
L.A. SVENSSON ◽  
L.D. COPE ◽  
J.L. LATIMER ◽  
E.J. HANSEN ◽  
...  


2001 ◽  
Vol 30 (3) ◽  
pp. 157-166 ◽  
Author(s):  
Liselott A. Svensson ◽  
Andrzej Tarkowski ◽  
Monica Thelestam ◽  
Teresa Lagergård




2005 ◽  
Vol 7 (5-6) ◽  
pp. 867-874 ◽  
Author(s):  
Catharina Wising ◽  
Lena Mölne ◽  
Ing-Marie Jonsson ◽  
Karin Ahlman ◽  
Teresa Lagergård


1999 ◽  
Vol 67 (12) ◽  
pp. 6394-6402 ◽  
Author(s):  
Valentina Gelfanova ◽  
Eric J. Hansen ◽  
Stanley M. Spinola

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.



Toxicon ◽  
2005 ◽  
Vol 45 (6) ◽  
pp. 767-776 ◽  
Author(s):  
Catharina Wising ◽  
Jozef Azem ◽  
Madeleine Zetterberg ◽  
Liselott A. Svensson ◽  
Karin Ahlman ◽  
...  


1999 ◽  
Vol 67 (8) ◽  
pp. 3900-3908 ◽  
Author(s):  
Marla K. Stevens ◽  
Jo L. Latimer ◽  
Sheryl R. Lumbley ◽  
Christine K. Ward ◽  
Leslie D. Cope ◽  
...  

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.



2001 ◽  
Vol 69 (3) ◽  
pp. 1938-1942 ◽  
Author(s):  
Royden S. Young ◽  
Kate R. Fortney ◽  
Valentina Gelfanova ◽  
Carrie L. Phillips ◽  
Barry P. Katz ◽  
...  

ABSTRACT Haemophilus ducreyi makes cytolethal distending toxin (CDT) and hemolysin. In a previous human challenge trial, an isogenic hemolysin-deficient mutant caused pustules with a rate similar to that of its parent. To test whether CDT was required for pustule formation, six human subjects were inoculated with a CDT mutant and parent at multiple sites. The pustule formation rates were similar at both parent and mutant sites. A CDT and hemolysin double mutant was constructed and tested in five additional subjects. The pustule formation rates were similar for the parent and double mutant. These results indicate that neither the expression of CDT, nor that of hemolysin, nor both are required for pustule formation by H. ducreyi in humans.



2003 ◽  
Vol 71 (11) ◽  
pp. 6633-6640 ◽  
Author(s):  
Kaiping Deng ◽  
Eric J. Hansen

ABSTRACT The cytolethal distending toxin (CDT) of Haemophilus ducreyi is comprised of the CdtA, CdtB, and CdtC proteins, with the CdtB protein having demonstrated enzymatic (i.e., DNase) activity. Using a single recombinant Escherichia coli strain with two plasmids individually containing the H. ducreyi cdtA and cdtC genes, we purified a noncovalent CdtA-CdtC complex. Incubation of this CdtA-CdtC complex with HeLa cells blocked killing of these cells by CDT holotoxin. Furthermore, the addition of purified recombinant CdtB to HeLa cells preincubated with the CdtA-CdtC complex resulted in the killing of these human epithelial cells.



Vaccine ◽  
2010 ◽  
Vol 28 (36) ◽  
pp. 5768-5773 ◽  
Author(s):  
Annika Lundqvist ◽  
Julia Fernandez-Rodrigues ◽  
Karin Ahlman ◽  
Teresa Lagergård


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