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Blocking Salmonella's access to nutrient could fight infection

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By Joe Whitworth+

Last updated on 31-Jul-2014 at 08:44 GMT

Picture: CDC/Salmonella
Picture: CDC/Salmonella

Salmonella relies heavily on a single nutrient during growth in the inflamed intestine and blocking access could fight infection.

The nutrient needed by Salmonella is composed of a sugar and amino acid stuck together, and is called fructose-asparagine (F-Asn).

It is the primary nutrient and if it cannot be obtained Salmonella becomes 1,000 times less effective at sustaining disease than when they’re fully nourished, according to research.

Blocking activation of one of five genes that transport the nutrient to Salmonella cells could be a strategy to fight infection.

‘Unfit’ Salmonella

“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.

Ahmer and colleagues found the food source by identifying the genes required to stay alive during the active phase of gastroenteritis, when the inflamed gut produces symptoms of infection.

The researchers ran 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.

“It has long been thought that the nutrient utilization systems of Salmonella would not make effective drug targets because there are simply too many nutrients available to Salmonella in the intestine,” said the researchers.

“Surprisingly, we have discovered that Salmonella relies heavily on a single nutrient during growth in the inflamed intestine, fructose-asparagine.

“A mutant of Salmonella that cannot obtain F-Asn is severely attenuated, suggesting that F-Asn is the primary nutrient utilized by Salmonella during inflammation.”

Surprise of sole nutrient

Ahmer said it was a ‘big surprise’ 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 fructose-asparagine, it’s really unfit.

“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.”

Because of that sole source for survival, the genes needed to acquire the nutrient could be effective drug targets.

This kind of drug also holds promise because it would affect only Salmonella and leave the trillions of other microbes in the gut unaffected.

Until the report, no organism had been shown to synthesize or utilize F-Asn, said the researchers.

Ahmer and colleagues are continuing to address the window of time in which access to the nutrient is most important for Salmonella’s survival and identifying human foods that contain high concentrations of fructose-asparagine.

Bacteria were mostly grown in Luria-Bertani (LB) broth or on LB agar plates and the minimal medium was NCE (no carbon E) containing trace metals.

Source: PLOS Pathogens

Online ahead of print, DOI: 10.1371/journal.ppat.1004209

“Fructose-Asparagine Is a Primary Nutrient during Growth of Salmonella in the Inflamed Intestine”

Authors: Mohamed M. Ali, David L. Newsom, Juan F. González, Anice Sabag-Daigle, Christopher Stahl, Brandi Steidley, Judith Dubena, Jessica L. Dyszel, Jenee N. Smith, Yakhya Dieye, Razvan Arsenescu, Prosper N. Boyaka, Steven Krakowka, Tony Romeo, Edward J. Behrman, Peter White, Brian M. M. Ahmer  

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