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A CdtA-CdtC complex can block killing of HeLa cells by Haemophilus ducreyi cytolethal distending toxin

Kaiping Deng1, Eric J Hansen

  • 1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9048, USA.

Infection and Immunity
|October 24, 2003
PubMed

Insights

The cytolethal distending toxin (CDT) from Haemophilus ducreyi comprises CdtA, CdtB, and CdtC proteins. Researchers purified a CdtA-CdtC complex that blocked cell killing by CDT holotoxin, but adding CdtB restored toxicity.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Toxinology

Background:

  • The cytolethal distending toxin (CDT) is a key virulence factor produced by several Gram-negative bacteria, including Haemophilus ducreyi.
  • CDT is a hetero-oligomeric protein complex composed of three subunits: CdtA, CdtB, and CdtC.
  • The CdtB subunit possesses DNase activity, which is crucial for the toxin's cytotoxic effects.

Purpose of the Study:

  • To investigate the roles of individual CDT subunits in the mechanism of cytolethal distending toxin.
  • To characterize the interaction between CDT subunits and their contribution to holotoxin activity.

Main Methods:

  • Recombinant Escherichia coli strains were engineered to express Haemophilus ducreyi cdtA and cdtC genes.
  • A noncovalent CdtA-CdtC complex was purified from the recombinant E. coli.
  • HeLa cells were treated with the purified CdtA-CdtC complex and/or recombinant CdtB to assess cell viability.

Main Results:

  • Purified CdtA-CdtC complex alone did not induce cell death in HeLa cells.
  • Preincubation of HeLa cells with the CdtA-CdtC complex blocked the cytotoxic effect of the CDT holotoxin.
  • Subsequent addition of purified recombinant CdtB to cells pretreated with the CdtA-CdtC complex restored the killing of human epithelial cells.

Conclusions:

  • The CdtA-CdtC complex acts as a neutralizer or inhibitor of the CDT holotoxin's cytotoxic activity.
  • The CdtB subunit is essential for the DNase activity and subsequent cell-killing function of the CDT holotoxin.
  • This study elucidates the distinct roles of CDT subunits in bacterial pathogenesis and provides insights into potential therapeutic targets.

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