A sugar and amino acid compound called fructose-asparagine never previously recognized as a nutrient for any organism is the stuff that makes Salmonella grow and it could be key to the pathogen’s demise. Brian Ahmer, associate professor of microbial infection and immunity at The Ohio State University, says the nutrient may be the Achilles’ heel for Salmonella and its 2,500 strains. It’s the single food source Salmonella need to remain strong inside the inflamed intestine. Blocking the activation of one of five genes that move the nutrient to Salmonella cells could be the way to fight the infection. That’s because when they are blocked and the Salmonella cannot get access to this nutrient, they becomes much times less effective at keeping the disease going than when fully nourished. “For some reason, Salmonella really wants this nutrient, and if it can’t get this one, it’s in really bad shape,” says Ahmer, commenting on the research recently published in the peer-reviewed, open-source journal PLOS Pathogens. The single nutrient, known as F-Asn, opens new pathways for fighting Salmonella because it opens up a weakness not previously seen in the pathogen that has long confounded science. “If you could block Salmonella from getting that nutrient, you’d really stop Salmonella,” Ahmer explains. Foods such as raw meat and raw eggs contaminated with Salmonella bring on Salmonellosis, a disease of the intestine. Symptoms usually occurring in 12 to 72 hours include diarrhea, fever, cramps, vomiting and headaches. Usually the illness last four to seven days, requiring only home care. However, Salmonellosis can require hospitalization. In rare cases, usually where the infection moves to the bloodstream from the intestine, it can be a cause of death. Salmonella has been a perplexing problem for both industry and government in the U.S. The Centers for Disease Control and Prevention (CDC) says that Salmonella causes 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths annually in this country. Risks from Salmonella are greater in underdeveloped countries where poor sanitation conditions exist. Because antibiotics kill both helpful and harmful bacteria, they are not usually used to treat Salmonellosis. The new research raises the possibility of making a drug to target the genes needed to acquire F-Asn to impede Salmonella growth while not impacting other gut bacteria. Scientists originally looked at five genes required by Salmonella for life during the active phase of gastroenteritis. They found the five worked together to move a nutrient into the bacterial cell and then broke it down for use as energy. Ahmer says it took “luck and guesswork” to see the links with genes in E. coli and to identify the nutrient as F-Asn. The researchers then experimented on cell cultures and mice to find out what happened when the genes were mutated. They found that Salmonella’s fitness to “survive, grow, and inflict damage” fell by 100 to 10,000 times if it was not able to gain access to the nutrient even when 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,” Ahmer says. “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 several questions still remain 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. The National Institute of Allergy and Infectious Diseases and the National Institute of General Medical Sciences supported the research with grant funding. Co-authors include Mohamed Ali, Christopher Stahl, Jessica Dyszel, Jenee Smith and Yakhya Dieye of microbiology; Juan Gonzalez, Anice Sabag-Daigle and Brandi Steidley of microbial infection and immunity; Judith Dubena, Prosper Boyaka and Steven Krakowka of veterinary biosciences; Razvan Arsenescu of internal medicine, and Edward Behrman of chemistry and biochemistry, all at Ohio State; Peter White and the late David Newsom of the Research Institute at Nationwide Children’s Hospital, and Tony Romeo of the University of Florida.