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Interdisciplinary Team Exploits Bacterium's Weakness Assisted by $2,608,207 NIH Grant

May 6, 2015

Interdisciplinary Team Exploits Bacterium's Weakness Assisted by $2,608,207 NIH Grant

Brian Ahmer

Although only 42,000 cases of salmonellosis — the infection caused by the bacterium Salmonella — are reported each year, the U.S. Center for Disease Control believes that cases are grossly underreported and estimates that Salmonella causes 1.2 million illnesses, 19,000 hospitalizations and 380 deaths every year.

We can count ourselves lucky if we have never been plagued by a Salmonella infection; even milder cases are no fun.

Now, for the next five years, a new NIH grant will allow an interdisciplinary team led by microbiologist Brian Ahmer joined by biochemists Venkat Gopalan, professor, chemistry and biochemistry; Edward Behrman, professor emeritus, chemistry and biochemistry; Vicki Wysocki, Ohio Eminent Scholar and professor, chemistry and biochemistry; and microbiologist Kelly Wrighton, assistant professor, microbiology.

They will be building on earlier research done by Ahmer, Edward Behrman and other colleagues. That research identified a potential chink in Salmonella’s armor — the bacterium’s reliance on a single food source to maintain fitness in an inflamed intestine.

They found that without access to this nutrient, the bacteria become 1,000 times less effective in sustaining disease. That nutrient, composed of a sugar and amino acid stuck together, is called fructose-asparagine — and — “It had never been discovered to be a nutrient for any organism,” Ahmer said.

That was a big surprise. Most bacteria can grow on many different nutrients. And while Salmonella can obtain hundreds of different nutrients readily available in the human gut, without fructose-asparagine, its effectiveness is substantially diminished. 

Because this is the sole source necessary for survival, the genes needed for acquisition of this nutrient might be effective drug targets.

“Nobody’s ever looked at nutrient transporters as drug targets because it’s been assumed that there will be hundreds more transporters, so it’s a pointless pursuit,” Ahmer said.

This kind of drug also could be promising because it would affect only Salmonella, leaving the trillions of other microbes in the gut unaffected.

“Since our team discovered that Salmonella thrives on this novel nutrient, fructose-asparagine (F-Asn), the goals of our new grant are to determine the enzymatic mechanisms used by Salmonella to grow on F-Asn and to learn which intestinal organisms compete with Salmonella for F-Asn and why they fail,” Ahmer said.

Attaining these goals, Ahmer explained, will facilitate high-throughput screens for inhibitors of these enzymes along with the development of novel probiotics that can prevent or treat Salmonella infections.

This interdisciplinary team draws on diverse, wide-ranging expertise and tackles questions from multiple approaches: Ahmer’s expertise is in Salmonella genetics and animal models; Gopalan’s in the enzymology of F-Asn utilization enzymes, Behrman’s in the synthesis of F-Asn and related compounds, Wysocki’s in the measurement of F-Asn and related compounds in the intestine, and  Wrighton’s in the metagenomic analysis of F-Asn utilization in the intestine.

Relief for Salmonella sufferers may be in sight.

—Sandi Rutkowski

From January 20th, 2015 onCampus Today