Salmonella bacteria — the main cause of food poisoning — use nutrients from our gut’s own resident microbes to grow.
Vanderbilt University Medical Center investigators have discovered that Salmonella-induced inflammation causes gut microbiota to break down and release the amino acid aspartate, which Salmonella uses to expand. The results were published in the journal Cell Host & Microbe.
“We describe a previously unexplored mechanism by which the intestinal pathogen Salmonella exploits the gut microbiota to acquire aspartate and support its growth in the inflamed gut,” said Mariana Byndloss, DVM, PhD, assistant professor of Pathology, Microbiology and Immunology. “Our discoveries may aid in developing novel strategies that target a pathogen’s metabolic adaptations to treat gastroenteritis.”
Salmonella in contaminated food cause about 1.35 million illnesses (diarrhea, stomach cramps, fever), 26,500 hospitalizations and 420 deaths in the United States every year, according to the Centers for Disease Control and Prevention. Children under age 5, adults over age 65 and people with weakened immune systems are at risk for severe infections, and treatment options are becoming limited as Salmonella antibiotic resistance increases.
Salmonella entering the gut spark an inflammatory host response.
“We know that inflammation changes the metabolic landscape of the gut, but the mechanisms linking these changes and pathogen expansion have remained unclear,” Byndloss said.
In the current study, the researchers demonstrate in a mouse model that inflammation induced by Salmonella infection increases intestinal levels of the amino acid aspartate — and that the increased levels depend on the presence of the resident microbiota.
The researchers found that reactive oxygen species produced during the host inflammatory response cause lysis of commensal microbes, resulting in the release of aspartate, and they demonstrated how Salmonella uses aspartate for its energy needs and outcompetes commensal intestinal bacteria.
“Our findings provide a fundamental advance in understanding how the intestinal pathogen Salmonella has evolved to use microbiota-derived metabolites to thrive in the inflamed gut,” Byndloss said. “The current work contributes to our team’s overall goal of identifying metabolic pathways in gut bacteria and in the host response to pathogens that will aid in the prevention of human disease.”
Woongjae Yoo, PhD, who was a postdoctoral fellow in the Byndloss lab, and graduate student Nicolas Shealy are co-first authors of the Cell Host & Microbe paper. The research was supported by the National Research Foundation of Korea, National Institutes of Health (grants T32ES007028, T32AI112541, F31AI161882, T32DK007673, P30058404, R01DK131104, R01AI168302), Howard Hughes Medical Institute (HHMI), The Pew Charitable Trusts and the Burroughs Wellcome Fund. Byndloss is an HHMI Freeman Hrabowski Scholar.
