January 30, 2022

The bacteria strains that cause common symptoms of food poisoning usually contain a toxin that can damage DNA of intestinal cells, which might trigger colon cancer, according to a study in mice by researchers at the Johns Hopkins Bloomberg School of Public Health (United States).

This discovery, published in the journal Cancer Discovery, raises the possibility that some of the approximately two million new cases of colorectal cancer produced each year in the world have its origin in food poisoning brief and apparently mild. It also points to the possibility of future drugs that prevent colorectal cancers by neutralizing the newly identified toxin, UshA.

Consequences of an infection

Previous research has suggested that certain bacteria residing in the gut can trigger colorectal cancer through persistent infections involving a chronic intestinal inflammation.

infections of short duration causing food poisoning, as the traveler’s Diarrhea, that usually resolve in one or two days, have been considered traditionally non-cancerous.

“We hope that this study will motivate other researchers to conduct epidemiological studies to investigate this possible relationship between the transient diarrheal infections and the development of colon cancer“, says the study’s lead author, Dr. Fengyi Wan.

The investigation

In the study, Wan’s team conducted experiments with a mouse model of transient bacterial diarrheal illness using the bacterium Citrobacter rodentium, which bears strong similarities to the Escherichia coli strains that cause diarrhea in humans.

The researchers found that Citrobacter infection rapidly caused strong signs of DNA damage to the cells of the intestinal lining of the mice.

The scientists also observed that the damage depended on a mechanism of the bacteria called the type 3 secretion system. This syringe-shaped appendage is used by some bacteria, such as Citrobacter and strains of E. coli’ causes diarrhea, to inject proteins into host cells. This mechanism facilitates growth and survival of invading microbes.

The researchers eventually came across a protein injected by T3SS, UshA, which is the responsible for DNA damage. They found that UshA, which can also be produced by ‘E. coli’ that causes diarrhoea, contains a short segment with enzymatic DNA breaking activity.

The role of this DNA-breaking element in the Citrobacter life cycle is still unclear. (In the study, suppressing it did not appear to harm the bacteria’s growth or survival.) But the researchers found evidence in their mouse study that UshA may have a definitely carcinogenic effect in the infected host.

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The scientists experimented with a line of genetically modified mice that develop colon tumors spontaneously, and found that infection of these mice with Citrobacter containing UshA drastically accelerated tumor development. In contrast, infection with a modified Citrobacter that lacks the UshA gene had virtually no effect on accelerating tumor development.

The researchers also found that the types of mutations in Citrobacter-accelerated colon tumors were very similar to those that have been cataloged in human colon tumors, once more underscoring the possible relevance to human health.