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Cytolethal distending toxin family members are differentially affected by alterations in host glycans and membrane

Aria Eshraghi1, Francisco J Maldonado-Arocho, Amandeep Gargi

  • 1Department of Microbiology, University of California, Los Angeles, California 90095, USA.

The Journal of Biological Chemistry
|April 14, 2010
PubMed

Insights

Cytolethal distending toxins (CDTs) from different bacteria vary in their ability to harm host cells. Cell surface sialic acid is crucial for intoxication by some CDTs, while other factors are less important.

Area of Science:

  • Microbiology
  • Cell Biology
  • Toxicology

Background:

  • Cytolethal distending toxins (CDTs) are bacterial exotoxins that cause DNA damage, cell cycle arrest, and apoptosis.
  • CDTs are produced by various Gram-negative pathogens and are thought to contribute to virulence by disrupting host cell functions.
  • Limited understanding exists regarding the specific host cell factors involved in CDT-mediated intoxication.

Purpose of the Study:

  • To investigate the differential abilities of CDTs from various bacterial species to intoxicate host cells.
  • To identify specific host cell surface molecules and cellular factors that mediate or influence CDT binding and intoxication.
  • To elucidate the molecular basis of CDT-host interactions and their variability.

Main Methods:

  • Testing the intoxication potential of CDTs from *Haemophilus ducreyi*, *Aggregatibacter actinomycetemcomitans*, *Escherichia coli*, and *Campylobacter jejuni* on host cells with defined genetic defects.
  • Evaluating the role of cell surface sialic acid, fucosylated N-linked glycans, glycosphingolipids, and host-cellular cholesterol in CDT intoxication.
  • Comparing the effects of these host factors across different CDT-producing bacterial species.

Main Results:

  • CDTs exhibited distinct intoxication capabilities, indicating variability in their interaction with host cells.
  • The absence of cell surface sialic acid significantly sensitized host cells to intoxication by three of the four tested CDTs.
  • Fucosylated N-linked glycans and glycolipids were not essential for intoxication by any of the tested CDTs.
  • Alterations in host-cellular cholesterol affected intoxication by only a subset of the CDTs.

Conclusions:

  • Host cell surface molecules, particularly sialic acid, play a critical role in mediating intoxication by specific CDTs.
  • The interaction of CDTs with host cells is complex and varies depending on the bacterial source and the specific host factors involved.
  • These findings provide crucial insights into the molecular mechanisms underlying CDT pathogenicity and host cell targeting.

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