Researchers may have found a major weakness in Salmonella bacteria, which could lead to new strategies to treat this infection.
A study published in PLOS Pathogens has found that a single nutrient, fructose-asparagine (F-Asn), is heavily relied upon when the Salmonella bacteria are growing.
When this nutrient cannot be accessed, the bacteria become much less effective at sustaining disease. This reliance could become a new target for therapies.
"If you could block Salmonella from getting that nutrient, you'd really stop Salmonella," says Prof. Brian Ahmer, lead author of the study and associate professor of microbial infection and immunity at Ohio State University.
Diarrhea, fever, cramps, vomiting
Salmonella bacteria cause an infection called salmonellosis that affects the intestine. The infection is normally caused by foods such as raw meat and raw eggs that have been contaminated by feces.
Stomach cramps are just one of the symptoms of Salmonella infection. Many recover without treatment, but for some it can become a severe illness.
Most people infected with Salmonella recover without treatment, but in severe cases it can result in hospitalization. The infection can spread from the intestine to the bloodstream, potentially infecting tissues throughout the body. In extreme cases, it is capable of causing death if treatment is not given.
The Centers for Disease Control and Prevention (CDC) report that Salmonella is estimated to cause around 1.2 million illnesses in the US every year, with about 23,000 hospitalizations and 450 deaths. In countries with poor sanitation, the risk of infection is much greater.
Unfortunately, antibiotics kill beneficial gut bacteria along with Salmonella, and so they are not recommended as a treatment method for most cases of salmonellosis.
However, if drugs were to target the genes needed for the acquisition of F-Asn, then this would affect the growth of Salmonella while leaving the rest of the other bacteria in the gut unaffected.
Initially, the researchers identified five genes required by Salmonella in order to stay alive during the active phase of gastroenteritis. They found that these worked together to transport a nutrient into the bacterial cell and broke it down so that it could be used for energy.
After seeing links with genes in E. coli. they eventually managed - with some luck and guesswork, according to Ahmer - to identify this particular nutrient as F-Asn.
The authors of the study then experimented on cell cultures and mice to find out what would happen when these genes were mutated. They found that Salmonella's fitness - its ability to survive, grow and inflict damage - dropped between 100-10,000 times if it was unable to access the nutrient. This was the case even when all its other sources of food were available.
"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," says Ahmer.
"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. In the gut, Salmonella can obtain hundreds of different nutrients. But without F-Asn, it's really unfit."
They may have reached this finding with the help of guesswork and luck, but there still remain several questions that will require hard work to answer. Future research from the team will examine the window of time in which access to F-Asn is most important for the bacteria's survival. They will also investigate which human foods contain high levels of the nutrient.
For now though, the authors say that the F-Asn utilization system represents a specific and potent therapeutic target for Salmonella.