CdtB

cdtB is the gene encoding the catalytic subunit of the cytolethal distending toxin (CDT) produced by several Gram-negative bacteria. In CDT operons, cdtA, cdtB, and cdtC encode the three subunits required for activity, with CdtB functioning as the enzymatic component that damages host DNA.

Biochemical activity and effects: CdtB is a Mg2+- or Ca2+-dependent DNase I–like enzyme that introduces double-strand breaks in host DNA. This DNA damage activates the host DNA damage response, leading to cell cycle arrest at the G2/M transition and, in some cells, apoptotic or senescent outcomes. The extent of cytopathic effect can vary by cell type and bacterial strain.

Delivery and mechanism of action: The CDT holotoxin binds to host cells via the CdtA and CdtC subunits, is internalized, and trafficked to the nucleus where CdtB exerts its nuclease activity. Proper delivery requires the presence of all three subunits.

Genetics and distribution: cdtB is found in a range of pathogenic bacteria, including Campylobacter species and certain Escherichia coli strains, often as part of the cdtABC operon on the chromosome or plasmids. The presence and expression of CDT genes vary among strains, and not all clusters encode functional toxins.

Clinical and pathogenic relevance: CDT has been associated with cytopathic effects in cultured cells and is considered a virulence factor in CDT-producing strains, contributing to gastrointestinal pathology and immune modulation in some infections. The role of CDT in disease is context-dependent and an area of ongoing research.

Relation and structure: CdtB shares homology with DNase I family enzymes and requires metal cofactors for catalysis; structural studies support a nuclease-like fold enabling DNA cleavage.