Cytolethal distending toxin

PDB protein 1sr4 (HdCDT)

Cytolethal distending toxin (CDT) is a bacterial toxin produced by several pathogenic bacteria, including but not limited to Escherichia coli, Campylobacter jejuni, and Salmonella species. CDT is a heterotrimeric toxin composed of three subunits: CdtA, CdtB, and CdtC. Each subunit plays a distinct role in the toxin's mechanism of action, with CdtB being the active enzyme component that induces DNA damage in host cells, leading to cell cycle arrest and apoptosis (cell death).

Mechanism of Action

The mechanism of action of CDT involves several steps. Initially, the CdtA and CdtC subunits bind to the surface of target cells, facilitating the entry of the CdtB subunit into the cell. Once inside, CdtB acts as a DNase, causing double-stranded breaks in the host's DNA. This DNA damage activates the cell's DNA repair mechanisms and leads to the activation of checkpoints that halt the cell cycle. If the damage is too severe and cannot be repaired, the cell undergoes apoptosis. The ability of CDT to induce cell cycle arrest and apoptosis makes it a potent cytotoxin.

Role in Disease

CDT is implicated in the pathogenesis of diseases caused by its producing bacteria. For example, in Campylobacter jejuni, one of the most common causes of bacterial gastroenteritis worldwide, CDT contributes to the severity of infection by damaging intestinal epithelial cells, leading to diarrhea, fever, and abdominal pain. Similarly, in Escherichia coli infections, CDT production is associated with increased virulence and the ability to cause severe intestinal and extra-intestinal diseases.

Detection and Research

Research into CDT has focused on understanding its structure, mechanism of action, and role in disease to develop targeted therapies and vaccines. Detection of CDT-producing bacteria involves a combination of culture techniques, PCR to identify the genes encoding the toxin, and assays to detect the toxin's activity in cell cultures.

Prevention and Treatment

Prevention of diseases caused by CDT-producing bacteria primarily involves proper food safety practices and water sanitation to reduce the risk of infection. Treatment of infections involves antibiotics, though the increasing prevalence of antibiotic resistance among these bacteria is a growing concern. Research into vaccines and targeted therapies against CDT is ongoing, with the aim of mitigating the toxin's effects in infected individuals.

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