Characterisation of cytolethal distending toxin (CDT) mutants of Campylobacter jejuni

D Purdy1, C M Buswell1, A E Hodgson1

  • 1Centre for Applied Microbiology and Research, Salisbury, Wiltshire, SP4 0JG.

Insights

Cytolethal distending toxin (CDT) is crucial for Campylobacter jejuni pathogenicity. CDT inactivation in C. jejuni mutants reduced cytotoxicity and impaired systemic invasion in mice, suggesting CDT is the primary toxin.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Campylobacter jejuni is a leading cause of bacterial gastroenteritis.
  • Cytolethal distending toxin (CDT) is a key virulence factor implicated in C. jejuni pathogenicity.
  • The precise role of CDT in C. jejuni pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the contribution of cytolethal distending toxin (CDT) to the toxigenicity and pathogenicity of Campylobacter jejuni.
  • To assess the impact of CDT inactivation on C. jejuni virulence in vitro and in vivo.

Main Methods:

  • Inactivation of the cdtB subunit in C. jejuni 81-176 and NCTC 11168 strains via insertional mutagenesis.
  • HeLa cytotoxicity assays using cell-free sonicates from isogenic cdtB mutant strains.
  • Oral administration of C. jejuni cdtB mutant strains to severe combined immunodeficient (SCID) mice to evaluate colonization and systemic invasion.

Main Results:

  • C. jejuni 81-176 cdtB- mutants showed significantly attenuated HeLa cytotoxicity but retained some toxigenicity.
  • C. jejuni NCTC 11168 cdtB- mutants exhibited no detectable cytotoxicity.
  • cdtB mutant strains were proficient in enteric colonization but showed reduced invasiveness into blood, spleen, and liver tissues in SCID mice.

Conclusions:

  • CDT appears to be the principal toxin contributing to Campylobacter jejuni pathogenicity.
  • Some C. jejuni strains may possess additional virulence factors distinct from CDT.
  • CDT plays a significant role in the systemic dissemination of C. jejuni infections.