Typhoid toxin increases host survival and promotes asymptomatic infection

DNA damage caused by bacterial genotoxins has been linked to cancer, but what, if any, function genotoxins have in the context of a natural infection is not clear. 

Teresa Frisan, from the Karolinska Institute in Stockholm, Sweden, and colleagues focused on the typhoid toxin from Salmonella enterica Typhi (S. Typhi), and specifically looked at chronic asymptomatic infection, which is known to increase the risk for tumors.

S. Typhi infects only humans, making it difficult to study in in vivo mouse models. To get as close as possibly in an animal model, the researchers developed two Salmonella enterica Typhimurium (S. Typhimurium) strains, which cause systemic typhoid fever-like infection in immunocompetent mice. In contrast to normal S. Typhimurium strains that do not harbor the genotoxin, the two strains were engineered to produce either an active or an inactive typhoid genotoxin.

The researchers infected mice orally with the two bacterial strains and--to their surprise--found that mice infected with the strain carrying the intact typhoid toxin had higher survival rates within the first 10 days post infection. None of the surviving mice from either group fell ill at later stages, but the mice infected with the toxigenic strain were more likely to develop chronic infection without disease signs.

The researchers conclude that their data "collectively highlight a novel aspect of typhoid toxin as an immune modulator, which reduces the intestinal inflammatory response and the clearance of the bacteria." Commenting on the potential link between genotoxins and cancer, they say "in our experimental conditions, chronic infection was not associated with induction of dysplasia or pre-carcinogenic lesions within the study period."