Pumping the brakes on Salmonella
Salmonellae—any of various rod-shaped bacteria of the genus Salmonella—are a leading cause of bacterial food-borne disease in the United States and the leading cause of death from bacterial foodborne disease. Each year about 1.2 million Americans get sick and about 450 die from salmonellosis, according to the Centers for Disease Control and Prevention (CDC).
Salmonellosis is a disease of the gastrointestinal system, and people with it display nausea, vomiting, diarrhea, abdominal cramps and sometimes fever. In healthy adults, the disease will usually go away on its own in four to seven days, but young children, older adults and anyone with a compromised immune system can develop serious disease that should be treated with antibiotics.
“Unfortunately, these drugs don’t seem to help much in uncomplicated salmonella infections,” said Lydia Bogomolnaya, PhD, research assistant professor in the laboratory of Helene Andrews-Polymenis, DVM, PhD, professor in the Department of Microbial Pathogenesis and Immunology at the Texas A&M College of Medicine who studies salmonella. “They don’t really shorten the duration of the symptoms, and patients treated with antibiotics often relapse.” It’s unclear why antibiotics show so little efficacy for this bacterial infection.
But a structure within the bacterial cell itself may hold the key to a solution.
The bacteria seem to resist antibiotics by ejecting the drug using special pump-like structures on their surface. “You treat the person, and the bacterial cells just pump the antibiotic out again,” Bogomolnaya said. Oddly enough, these structures that pump out antibiotics seem to be ancient, while the use of antibiotics for treating bacterial infection is relatively modern. Therefore, Bogomolnaya’s research in the Andrews-Polymenis laboratory focuses on why these structures are needed in the absence of antibiotic treatment. “If we can understand what they’re doing, we can get a better idea of how to prevent antibiotic resistance.”
There are at least 11 of these types of pumps in salmonella, but Bogomolnaya focuses on the one that also plays a role in virulence, or harmfulness, of the pathogen. “If you block this one pump, salmonella cannot cause disease like it would otherwise,” she said. It seems that in the absence of antibiotics, these pumps help the bacterium protect itself from oxidative stress—in other words, the sort of conditions in the gut of an animal suffering from a salmonella infection. “If this gut inflammation occurs, and the pump isn’t working, the salmonella will die.”
Bogomolnaya hopes that by understanding molecular mechanism behind how the pump works, researchers will be able to come up with a way to stop it from working, rendering the bacteria harmless. These pumps are not solely present in salmonella; many other pathogens—including infectious strains of E. coli—have similar structures. Therefore, Bogomolnaya and her colleagues hope that at some point in the future, they could apply similar techniques to other bacteria to better control infections.
Bogomolnaya started at Texas A&M as a postdoctoral researcher in the lab of Andrews-Polymenis, who has a joint appointment in the Texas A&M College of Veterinary Medicine & Biomedical Sciences, and is currently a research assistant professor in the Andrews-Polymenis laboratory.
“This research is exciting because I see a direct application to human health,” Bogomolnaya said. “There’s been so much work done in everything from microbiology to food safety, but the number of cases doesn’t seem to be changing. It clearly requires a better understanding on our side of how this pathogen can infect us and how we can reduce salmonella cases in humans and livestock.”