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New defense discovered against common hospital-acquired infection
Date:8/21/2011

GALVESTON Researchers have discovered a key mechanism used by intestinal cells to defend themselves against one of the world's most common hospital-acquired bacterial infections a mechanism they think they can exploit to produce a therapy to protect against the effects of the antibiotic-resistant bacteria.

The scientists made their discovery while investigating cellular responses to two powerful toxins generated by the bacteria Clostridium difficile, which can cause symptoms ranging from diarrhea to life-threatening bowel inflammation.

"About one percent of all hospital patients develop a C. difficile infection they're treated with antibiotics to the point that benign gut bacteria are knocked out, and because C. difficile is resistant to antibiotics it's able to proliferate," said University of Texas Medical Branch at Galveston associate professor Tor Savidge, lead author of a paper on the discovery to be published online Aug. 21 in Nature Medicine. "Then it releases these toxins that trigger colonic disease."

The toxins wreak havoc on cell structural proteins and biochemical communications networks, eventually killing the cell. But in order to do this damage, the toxins first have to get into the cell, and that means passing through the protective membrane that surrounds it.

It's there that Savidge and his collaborators a multidisciplinary team of researchers from UTMB, UCLA, Case Western Reserve University, Tufts University and the Commonwealth Medical College may have found a way to stop them.

On the molecular scale, C. difficile toxin proteins are quite large big enough that they have to "cleave" so that a smaller piece can slip through the membrane and into the cell. This cleavage is accomplished by a built-in molecular guillotine called a cysteine protease, which activates when the toxin encounters a molecule called InsP6 that is present at much higher levels inside the cell tha
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Contact: Jim Kelly
jpkelly@utmb.edu
409-772-8791
University of Texas Medical Branch at Galveston
Source:Eurekalert

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