Toxin making S.enterica typhi Actually Helps Mice in Survival !
The bacterium Salmonella enterica Typhi causes typhoid fever in humans and produces a DNA-damaging protein called typhoid toxin. A new study suggests that typhoid toxin appears to prolong survival and reduce gut inflammation in S.enterica-infected mice.
An international team of researchers while working on cancer, modified mouse S.enterica with typhoid toxin genes from the human-infecting strain responsible for the high fever, headache and rash of typhoid fever as the deadly, mouse-infecting version of S. enterica doesn’t normally make the typhoid toxin. The team thought that typhoid toxin’s DNA slashing might cause tumors, but in mice fed with the toxin-making S. enterica, no increased cancer risk appeared compared with mice given the toxin-free microbes. To the researchers’ surprise, though, more mice with the toxin survived 20 days of infection than did mice with the toxin-free strain.
When I first saw the data on the survival of the mice, I said, ‘No, we mixed up the strain,’ because we were expecting exactly the opposite,” says study coauthor Teresa Frisan, a cellular microbiologist at the Karolinska Institute in Stockholm. “We were chasing cancer, and we found biology of the toxin.” Mice infected with
the typhoid toxin-making strain also had less intestinal inflammation after 10 days. Several genes linked to inflammation and immunity became less active after exposure to the toxin-making microbes, an international team of researchers reported in PLOS Pathogens.Increased survival and decreased immunity may extend S. enterica’s stay within its host’s body. After six months, mice that survived infection with the typhoid toxin-free strain had no detectable S. enterica in their livers. But five out of six mice infected with the toxin-making strain still had substantial amounts of the bacteria in their livers. These results suggest that typhoid toxin promotes long-term, symptom-free infections, the researchers say.
Distinct differences exist between the mouse-infecting and human-infecting strains of S. enterica, even with the modifications made in the study, Jones says. Such differences could limit the clinical applicability of the results. But future studies could explore the possibility of disabling typhoid toxin to bolster an infected animal’s immune defenses, Jones says. But given the toxin’s apparent ability to keep infected animals alive — and infectious bacteria around — the team suggests that the label of “toxin” may actually be undeserved.
