Exploring the undiscovered mechanics of Salmonella infection

To fully understand how Salmonella survives in different environments and causes infection, researchers have to understand the functions of all Salmonella genes—much like a mechanic has to know the function of each car part to know how a vehicle works.

However, imagine taking your car to an automotive care center to find that the mechanic only knows the function of a third to half of your car’s parts. With limited information on the mechanical functionality of your car, it is likely that the mechanic will struggle to fix your vehicle.

While mechanics know the function of most (if not all) car parts, researchers who study Salmonella genes, such as Helene Andrews-Polymenis, DVM, PhD, see this automotive analogy as a reality in their field. About a third to a half of the 4,500 genes in Salmonella don’t have a known function, Andrews-Polymenis said. Filling in this knowledge gap could lead to strategies to prevent Salmonella infection.

“Bacteria have to survive in all kinds of different environments, such as in the soil, in your gut or on your skin,” Andrews-Polymenis explained. “Understanding all the genetic tools that bacteria have to survive in different environments is important, because then you can design interventions to stop the bacteria from causing infection.”

The importance of reducing Salmonella infections

In general, individuals exposed to Salmonella develop diarrhea, abdominal cramps and fever. Healthy individuals are usually able to recover from Salmonella infection within about a week without specific treatment. However, for children, the elderly and immunocompromised individuals, the risk of developing Salmonella infection is higher and could lead to life-threatening conditions, according to the Mayo Clinic.

Reducing Salmonella infection in humans and livestock remains a nationwide goal. In fact, in January 2000, the Department of Health and Human Services launched Healthy People 2010, which included a goal of reducing Salmonella infection cases in humans by 50 percent.

However, by 2010 the United States had not reached that national goal. Numbers of Salmonella infection climbed as high as 17.6 cases per 100,000 people, far from the goal of 6.8 or fewer cases per 100,000 people, according to FoodNet, a collaborative program among the Centers of Disease Control and Prevention (CDC), 10 state health departments, the U.S. Department of Agriculture’s Food Safety and Inspection Service and the Food and Drug Administration. Today, the CDC estimates an annual incidence of 15.2 Salmonella infection cases per 100,000 people. Although cases have slightly decreased, Andrews-Polymenis believes this rate can decrease even more with proper intervention strategies.

“Reducing Salmonella cases is important because Salmonella is the most prevalent cause of foodborne bacterial disease that is fatal in the United States,” Andrews-Polymenis said.

The CDC estimates that 450 deaths occur annually in the United States due to Salmonella infection. Unlike other bacterial infections, antibiotics are not commonly used to treat Salmonella infection because these drugs don’t reduce the severity of the disease or duration that infected persons can spread the disease to others, Andrews-Polymenis said. Only in severe cases, such as when Salmonella spreads from the intestines to the blood stream, are antibiotics used to treat Salmonella infection, according to the Mayo Clinic. Therefore, with few treatment options, intervention strategies to decrease exposure to Salmonella are key in lowering the number of Salmonella infections.

However, Andrews-Polymenis’ research could change this lack of treatment options for Salmonella infections. If new genes that play a role in Salmonella infection are identified, more effective antibiotics could be developed to target those new genes and help decrease the duration and severity of Salmonella infection.

“Contributing to creating new, effective vaccines or antibiotics to reduce the burden of Salmonella infection is our long-term goal,” Andrews-Polymenis said.

Investigating Salmonella genes

Preventing Salmonella infection is the focus of Andrews-Polymenis’ research. As a professor in the Texas A&M College of Medicine, with a secondary appointment in the College of Veterinary Medicine & Biomedical Sciences, Andrews-Polymenis is dedicated to reducing Salmonella infections in both humans and livestock by exploring the unknown functions of Salmonella genes. By better understanding the functions of Salmonella genes, Andrews-Polymenis hopes to develop strategic interventions to prevent Salmonella infection.

In her research, Andrews-Polymenis has created a collection of “mutant” variants of S. typhimurium, which is a strain of Salmonella. Each variant is missing a single gene, and the collection of mutant variants she has created contains 3,800 such strains, each missing a different gene. This collection of mutant variants is used in Andrews-Polymenis’ research to identify which genes in Salmonella are required to cause infection in different environments, including in the gut of an animal.

“When particular mutants do not survive in an animal, it means we removed a gene that was important for that variant to survive in the niche we are studying,” Andrews-Polymenis said. “Therefore, that gene could potentially play a role in that bacteria’s ability to cause infection.”

If the results with a given mutant are repeatable in multiple animals, chances are that gene has a significant role in causing Salmonella infection.

“That’s when we know if we should be hanging our hat on a certain gene of interest,” Andrews-Polymenis said.

Once genes that play a role in Salmonella infection are identified, this information provides the opportunity to focus on what those genes are doing during infection, and ultimately plays a critical role in developing intervention strategies that will target those genes and theoretically prevent or eliminate infection.

“Interventions are developed based on what genes the bacteria are depending on to live in a certain environment,” Andrews-Polymenis explained. “For example, if bacteria are feeding on something in the environment to stay alive, you could interfere specifically with the organism’s metabolism. This may give you an opportunity to reduce bacterial infections.”

Understanding how Salmonella genes play a role in infection is also critical in another part of Andrews-Polymenis’ research. She is using her knowledge of Salmonella gene function to study how and why Salmonella rapidly colonizes in the gut of young chickens.

“When chickens are three to four days old, they can become colonized with Salmonella in the intestine without developing illness,” Andrews-Polymenis said. “This is a frustrating problem because it’s really hard to eliminate Salmonella from chicken populations if the birds don’t appear to be ill. In addition, when chickens are infected with Salmonella at this age, they are infected for life. That’s one way Salmonella-infected poultry ends up in grocery stores.”

Identifying which genes in the bacteria potentially play a role in this rapid colonization in the gut of young chickens will help Andrews-Polymenis develop intervention strategies that will decrease the risk of Salmonella coming into contact with humans.

Could a host’s genetics play a role in Salmonella infection?

In collaboration with researchers across the Texas A&M campus, including David Threadgill, PhD, Andrews-Polymenis is also taking a different approach in her research. She is shifting the focus from Salmonella genes to the genes of the host, or the individual infected with Salmonella. The hosts’ genes may affect whether or not an individual develops Salmonella infection when exposed to the bacteria. By using a genetically diverse population of host animals, she hopes to better understand how host genetics affect disease outcome.

“It would be great to be able to predict who would be more susceptible or resistant to Salmonella infection based on genetics,” Andrews-Polymenis said.

Furthermore, exploring how an individual’s genes affect Salmonella infection could lead to individualized treatment. If an individual is exposed to Salmonella and doctors know how their genes affect disease outcome, they could intervene in a specific way that is most effective in treating Salmonella infection in that individual.

“Personalized medicine seems like it’s far into the future, but it might be just around the corner,” Andrews-Polymenis said.

Committed to her work

Working with bacterial diseases for over 20 years, Andrews-Polymenis knows the value of hard work and patience. Exploring the undiscovered functions of Salmonella genes may be challenging, but Andrews-Polymenis is dedicated to identifying effective intervention strategies to decrease Salmonella infection cases in both humans and livestock.

“My research has the potential to save lives by contributing to developing new strategies for prevention and treatment of Salmonella infection,” Andrews-Polymenis said.

Article written by Callie Rainosek