Cytolethal distending toxin

Cytolethal distending toxins (abbreviated CDTs) are a class of heterotrimeric toxins produced by certain gram-negative bacteria that display DNase activity. These toxins trigger G2/M cell cycle arrest in specific mammalian cell lines, leading to the enlarged or distended cells for which these toxins are named. Affected cells die by apoptosis. Cytolethal distending toxins (abbreviated CDTs) are a class of heterotrimeric toxins produced by certain gram-negative bacteria that display DNase activity. These toxins trigger G2/M cell cycle arrest in specific mammalian cell lines, leading to the enlarged or distended cells for which these toxins are named. Affected cells die by apoptosis. Each toxin consists of three distinct subunits named alphabetically in the order that their coding genes appear in the cdt operon. Cytolethal distending toxins are classified as AB toxins, with an active ('A') subunit that directly damages DNA and a binding ('B') subunit that helps the toxin attach to the target cells. CdtB is the active subunit and a homolog to mammalian DNase I, whereas CdtA and CdtC make up the binding subunit. Cytolethal distending toxins are produced by gram-negative pathogenic bacteria from the phylum Proteobacteria. Many of these bacteria, including Shigella dysenteriae, Haemophilus ducreyi, and Escherichia coli, infect humans. Bacteria that produce CDTs often persistently colonize their host. The first recorded observation of a cytolethal-distending toxin was in 1987 in a pathogenic strain in E. coli isolated from a young patient. Later that year, scientists W.M. Johnson and H. Lior published the journal article “Production of Shiga toxin and a cytolethal distending toxin (CLDT) by serogroups of Shigella spp.” In Microbiology Letters. The discovery of other bacteria producing CDT toxins continues to this day. In 1994 two scientists, Scott and Kaper, successfully cloned and sequenced a cdt operon from another E. coli strain, publishing their accomplishment in Infection and Immunity. The three genes discovered were denoted cdtA, cdtB, and cdtC. In 1997, the first paper of many to show G2/M cell cycle arrest caused by a cytolethal distending toxin was published in Molecular Microbiology. The study focused on another E. coli strain. This paper was followed by a 1999 publication in Infectious Immunity, which demonstrated that H. ducreyi CDT causes cell death via apoptosis. This finding was also confirmed for other cytolethal distending toxins in subsequent studies. The discovery of the homology of cdtB to mammalian DNase I and the current AB model for the toxin were published in early 2000. Further research and the publication of crystal structures for the CDT toxins from two different species continues to support this model. All known cytolethal distending toxins are produced by gram-negative bacteria in the gamma and epsilon classes of the Proteobacteria phylum. In several cases, the bacteria producing CDT are human pathogens. Medically important CDT producers include: CDT-producing bacteria are often associated with mucosal linings, such as those in the stomach and intestines, and with persistent infections. The toxins are either secreted freely or associated with the membrane of the producing bacteria.