Health & Environment

Prone To Sickness? Blame Your Genes

March 21, 2017

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By Christina Sumners, Texas A&M University Health Science Center

When a soldier in the field is exposed to an infectious agent, it’s a race against time to get him or her back to a hospital for care. But what if that ticking clock could be paused, or at least extended?

That’s the hope of a new $3.2 million grant from the Department of Defense’s Defense Advanced Research Projects Agency (DARPA). The researchers—led by two from the Texas A&M College of Medicine—are interested in finding ways to delay the onset of severe symptoms due to infectious agents the military might encounter in the field.

The team is focusing on three major infections: methicillin-resistant Staphylococcus aureus (MRSA), Salmonella typhimurium and Salmonella typhi. For each, infections can lead to severe illness and be potentially deadly.

Co-led by David Threadgill, PhD, a university distinguished professor in the Department of Molecular & Cellular Medicine and the Department of Veterinary Pathobiology, and Helene Andrews-Polymenis, DVM, PhD, associate professor in the Department of Microbial Pathogenesis and Immunology, the team at the College of Medicine is focusing on host tolerance mechanisms. “We want to understand what makes some people tolerant to infectious agents,” Threadgill said. “In other words, why do some people who are exposed not develop severe symptoms until a much later time?”

After ruling out possible differences in age and level of exposure—which are known to make a difference in whether an individual becomes symptomatic—Threadgill wants to look for individuals who are resistant to becoming ill or who become ill much later or much less severely. “We’re making the argument that these are probably genetic factors,” Threadgill said. “These factors could be mediated through the immune system, or it could be differences in other aspects of the infection process.”

These genetic factors that determine susceptibility to infection are likely distributed, to a greater or lesser extent, throughout a population.

“An example is the recent Ebola outbreak,” Threadgill said. “Epidemiological studies of infection outbreaks find that there were subsets of people who typically have a much-delayed response to the infectious agent and less severe symptoms.” It seems to be genetic diversity that explains why some people get very sick and die and others—who had the same standard of care—get very sick and get better, while others who are exposed either don’t get sick at all or who suffer only relatively mild symptoms.

Interestingly, when a unique population of animal models, developed by Threadgill, that mirrors human populations is challenged, the animal model responds very similarly. “At least the pilot experiments for other infectious agents the animal model population looked just like human populations, with the frequency of individuals essentially the same as was observed in humans.”

The major infectious agent the researchers are studying is MRSA, a particular interest of Andrews-Polymenis. MRSA is commonly thought of as a hospital-acquired infection, but it can also be acquired elsewhere. In fact, a prime location for MRSA outbreaks is military training camps.

“MRSA can be carried by normal, healthy individuals and spread in situations where individuals live in close contact. It is resistant to treatment with some antibiotics and can cause fatal infections,” Andrews-Polymenis said. “These factors make it likely to be a danger to warfighters.”

Once the researchers find which individuals within a population are more tolerant, they will study their genetic makeup to determine why they are not as affected—and from there, the next step would theoretically be a possible treatment.

“Soldiers in the battlefield are the primary driver of this research, but there are broader implications and groups of people who would benefit from understanding this better,” Threadgill said. “Identifying mechanisms that delay severity may lead to ways to therapeutically induce tolerance in non-tolerant individuals or even create preventative agents for those working in high-risk environments.”

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This story by Christina Sumners was originally posted on Vital Record.

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