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Penn Vet study reveals Salmonella's hideout strategy
Date:5/15/2014

nflammasome activation," Brodsky said.

To identify the mechanism by which the bacteria might do this, Brodsky's team made a library of Salmonella mutants, looking for those that might be involved in the evasion strategy.

Among the 18 genes they pinpointed were four that had been previously noted to have a role in enabling Salmonella strains to cause long-term, chronic infections.

"That was interesting because it suggested that at least a subset of those genes that might be important for long-term infection might be involved in evading or suppressing the inflammasome response," Brodsky said.

They trained their attention on one of these four, the gene that encodes the enzyme aconitase. Aconitase, which converts citrate to isocitrate, is a key component in the metabolic process known as the citric acid or Krebs cycle. This cycle is used by all oxygen-breathing organisms to convert sugar into energy and to produce important molecules for cell growth.

When the aconitase gene was mutated, the inflammasome known as NLRP3 was highly activated, leading researchers to believe that the normal version of aconitase might do the opposite, inhibiting the inflammasome. Moreover, when the researchers infected mice with a strain of Salmonella that had a mutated version of aconitase, the rodents were able to clear the infection, likely due to the inflammasome being activated. This infection led to increased levels of inflammation in the mice's tissues.

The Penn-led team also wanted to see whether other components of the citric acid cycle might be involved in inflammasome activation. They found that mutating Salmonella genes that encode two other players in the cycle, the enzymes isocitrate dehydrogenase and isocitrate lyase, also led to higher activation of the NLRP3 inflammasome.

In their normal state, these enzymes break down citrate. Thus the study's results point to the possibility
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Contact: Katherine Unger Baillie
kbaillie@upenn.edu
215-898-9194
University of Pennsylvania
Source:Eurekalert

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