Ohio State University (OSU) researchers have discovered that salmonella’s appetite and reliance on a single food source could be the bacteria’s downfall.
According to an OSU press release, researchers discovered that when the salmonella bacteria can’t access the nutrient fructose-asparagine, they become 1,000 times less effective at sustaining disease than when they're fully nourished.
The research suggests that blocking activation of one of five genes that transport the nutrient to salmonella cells could be a new strategy to fight infection.
“For some reason, salmonella really wants this nutrient, and if it can't get this one, it's in really bad shape,” said Brian Ahmer, associate professor of microbial infection and immunity at The Ohio State University and lead author of the study. “If you could block salmonella from getting that nutrient, you'd really stop salmonella.”
The research is published in the journal PLOS Pathogens.
Generally, most of the 42,000 Americans who report salmonella infection annually ride out the gastroenteritis symptoms of diarrhea, fever, stomach cramps and vomiting for four to seven days, according to the Centers for Disease Control and Prevention. Antibiotics aren’t a recommended treatment for most infections because they kill good gut bacteria along with salmonella.
Fructose-asparagine is composed of a sugar and amino acid stuck together. Its identification alone is also unusual: “It has never been discovered to be a nutrient for any organism,” Ahmer said.
Ahmer and colleagues found this important food source by first identifying the genes that salmonella requires to stay alive during the active phase of gastroenteritis, when the inflamed gut produces symptoms of infection.
The researchers ran numerous experiments in cell cultures and mice to observe what happened to salmonella in the inflamed gut when these genes were mutated. Under differing conditions, salmonella's fitness dropped between 100- and 10,000-fold if it could not access fructose-asparagine, even if all of its other food sources were available.
"That was one of the big surprises: that there is only one nutrient source that is so important to salmonella. For most bacteria, if we get rid of one nutrient acquisition system, they continue to grow on other nutrients," Ahmer said. "In the gut, salmonella can obtain hundreds of different nutrients. But without fructose-asparagine, it's really unfit."
Because of that sole source for survival, the genes needed for acquisition of this nutrient could be effective drug targets.
"Nobody's ever looked at nutrient transporters as drug targets because it's assumed that there will be hundreds more transporters, so it's a pointless pursuit," Ahmer said.
This kind of drug also holds promise because it would affect only salmonella and leave the trillions of other microbes in the gut unaffected.
Ahmer and colleagues are continuing this work to address remaining questions, including the window of time in which access to the nutrient is most important for salmonella's survival as well as identifying human foods that contain high concentrations of fructose-asparagine.
This work was supported by grants from the National Institute of Allergy and Infectious Diseases and the National Institute of General Medical Sciences.