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Scientists identify new strategy to fight deadly infection in cystic fibrosis
Date:1/23/2013

COLUMBUS, Ohio New research suggests that lowering excessive levels of a protein in immune system cells could be a strategy to clear an infection that is deadly to patients with cystic fibrosis (CF).

Researchers determined that normalizing levels of the protein, called p62, in cells from mice carrying the most common mutation that causes CF will jump-start a natural cellular process that clears away the offending bacteria.

The scientists had previously determined that in cells from mice and humans carrying the CF mutation, the bacteria that cause this infection interfere with an important survival process in immune system cells; they also attributed this interference to elevated levels of p62.

The survival process, called autophagy, allows a cell to digest parts of itself to produce energy when it is experiencing starvation. In many infections, autophagy also helps digest pathogens and clear them away.

The bacterium, Burkholderia cenocepacia, causes a severe and persistent lung infection in patients with CF and is resistant to nearly all known antibiotics. Various types of chronic lung infection are responsible for about 85 percent of deaths in CF patients.

"Autophagy also controls inflammation, so when you decrease p62 levels in a CF mouse model and that improves autophagy, you are controlling inflammation produced by Burkholderia cenocepacia. And that's what we are trying to do for patients save them from inflammation," said Amal Amer, associate professor of microbial infection and immunity and internal medicine at Ohio State University and senior author of the study.

While relatively rare, B. cenocepacia infection is highly transmissible in patients with cystic fibrosis. By causing either severe sepsis or massive inflammation that damages lung tissue, the infection amounts to a death sentence for CF patients.

To lower p62 levels, the researchers introduced a small interfering RNA molecule, or
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Contact: Amal Amer
amal.amer@osumc.edu
614-247-1566
Ohio State University
Source:Eurekalert

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