Bacteria that Cause Food Poisoning Contain Toxins That Destroy DNA, a Yale Study Shows

Protein toxins found in bacteria that are the most common culprit in food poisoning attack and destroy DNA, a study by Yale researchers shows.

The finding, published in the journal Science, is significant because little is known about how these bacteria cause disease, said the authors of the study, Jorge Galan, the Lucille P. Markey Professor of Microbiology and chairman of the Department of Microbial Pathogenesis at Yale School of Medicine, and Maria Lara-Tejero, a graduate student in the Yale microbiology graduate program.

“This toxin may help these bacteria to colonize the intestine,” the researchers said. “In addition, the presence of a bacterial toxin capable of causing DNA damage in a commonly occurring intestinal pathogen such as Campylobacter jejuni may constitute a predisposing factor for intestinal cancer.”

Campylobacter jejuni is the most common cause of food-borne infectious illnesses in the United States. This bacterial pathogen encodes a toxin known as cytolethal distending toxin (CDT), which is considered to be an important virulence factor. The CDT causes eukaryotic cells, which contain DNA in their membrane-enclosed nuclei, to stop dividing, although their cytoplasm, which is the contents of the cell excluding the nucleus, continues to grow and distend.

Galan and Lara-Tejero investigated which of the three CDT subunits - CdtA, CdtB, or CdtC - showed evidence of toxic activity within the host cell. While cells expressing CdtA and CdtC showed no signs of toxicity, cells expressing CdtB exhibited striking alterations characterized by fragmented nuclei, the researchers found. The changes were apparent as early as 18 to 24 hours after infection. Forty-eight hours later, the nuclei of the affected cells appeared seriously compromised.

The investigators found strong similarities between CdtB and DNAse I, a cellular enzyme that can destroy DNA. Consistent with this similarity, purified CdtB was shown to be able to attack DNA in the test tube. When injected in small amounts into cells, CdtB by itself was able to cause the cells to stop dividing and grow in size, just as if they were treated with the whole toxin. The researchers also found that cell division stops at a particular phase of the cell cycle as a result of control mechanisms triggered in the poisoned cell by the CdtB DNA damaging activity.

These studies may lead to the development of novel therapeutic strategies and may stimulate additional research to examine the potential of Campylobacter jejuni infections as a predisposing factor for intestinal cancer, said Galan and Lara-Tejero.