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DNA May Determine Who Gets Sick

Immunity genes could protect some from E. coli while others fall ill

Some patrons who dined at a trendy Mexican fast-food restaurant last year merely left with full stomachs; others left with an unwelcomed side order of Escherichia coli (E. coli). The spread of infection has made spicy headlines since the October 2015 outbreak was traced to contaminated Chipotle restaurants. The chain is trying to rehabilitate its brand, while instituting new food-safety protocols, paid sick leave to ill employees and DNA-based testing of selected ingredients to make sure they're safe before they ever reach restaurants.

An interesting question remains: Why did some patrons and employees become sick when exposed to E. coli, while others remained healthy? Similarly - and more commonly - when one child comes home from preschool with a stomach bug, why do some members of a family get sick while others remain healthy?

Genes May Make the Difference
It's a question that may be answered by a recent study (published Jan. 19 in the Journal of Infectious Diseases) from investigators at Duke University in collaboration with researchers from Durham (N.C.) VA Medical Center and Johns Hopkins University. They found that an individual's resistance to certain germs, E. coli bacteria in particular, could come down to DNA.

According to information provided by Duke Health, the researchers first exposed 30 healthy adults to enterotoxigenic E. coli, one of the world's leading causes of bacteria-induced diarrhea and "traveler's diarrhea," which often requires antibiotic treatment. woman cutching stomach

"To learn more about why some patients get sick and others stay well, the researchers drew patients' blood and looked for clues in their gene expression - the degree to which some genes are turned on or off," explained the Duke news release. "They noted differences among six patients with severe symptoms and six participants who showed no symptoms, despite having been exposed to the bacteria."

Among the thousands of genes that distinguished the two groups, there were significant differences in the activity of 29 immune-related genes that could predict who would go on to become sick and who would not, said senior author Ephrain Tsalik, PhD, assistant professor of medicine at Duke.

"Within each group there were changes in the patients' gene-expression patterns throughout the experiment," Tsalik said. "We found there were differences in the subjects that seemed to predict who would become sick. We interpreted those as signals that show an innate resistance to infection. There may be certain genetic traits that can increase or decrease your chances of being infected after exposure to a pathogen."

Some Patients More Susceptible
When asked if it is then safe to say that some patients just pick up bugs more readily than others, Tsalik told ADVANCE, "Yes, that is a reasonable conclusion and one supported by other research we've done with respiratory viruses including influenza, rhinovirus, and RSV. In each of these cases, as with the E. coli study, there are people who get exposed and harbor the bug yet they remain healthy."

But he cautioned, "Although there are indications that genetics plays a role, it is far more complicated than that. For example, the environment certainly plays a role. Poor hand hygiene, such as [lack of] hand-washing among healthcare providers, does increase the risk of infection. That's why phrases like 'cover your sneeze,' 'cough into your elbow' and similar mantras are still relevant. As to the genetics, we've shown that the activity of certain genes is different in resilient individuals. What we don't yet know is whether those differences are inherited or whether gene activity is shaped by our prior exposures or infections."

The Next Step
Because this study has been limited to E. coli, Tsalik said it is still unknown if the genes identified are relevant to other types of infection. "All we can say currently is that they are important in E. coli-induced diarrhea. It may be the case that some or all of these genes are important in infections more generally. That has yet to be determined and is precisely one of our active areas of research," he said. "Assuming, however, these findings are shown to be more broadly relevant, they can be used to identify patients at risk for illness given pathogen exposure. And it also gives us something to target for new treatments that aim to convert a susceptible person into a resilient one. It potentially opens up a whole new area for the development of new treatments."

SEE ALSO: Earn CE: Rapid Trauma Assessment

One may rightly wonder if information surfaced in this study could have helped in the Chipotle outbreak in any way. Tsalik weighed in on that point. "There are a few findings in this research that could be relevant to such a situation. First is the recognition that some people may harbor and shed the bacteria without even being sick. So just because an employee is feeling well, that doesn't mean they pose zero risk to those around them," he explained.

"Second, we have shown in this context as well as in other studies (influenza, RSV, and rhinovirus) that we can detect changes to a patient's gene-expression signature before symptoms are peaking. Those findings can be used to generate a test that will predict who will go on to become sick following an exposure, even if that person is feeling fine now," noted Tsalik. "We are actively working on developing such tests in a way that a care provider could have a result in an hour or less using a few drops of blood."

Valerie Newitt is on staff at ADVANCE. Contact: vnewitt@advanceweb.com.


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