Natural defense mechanism may fight antibiotic-resistant bacterial infection
New treatment stimulates the body to prevent C. difficile cells from cutting themselves into smaller bits, limiting the cells' ability to infect the intestine.
Sun, Aug 21, 2011 at 01:02 PM
Photo: Wikimedia Commons
CHICAGO - A natural defense mechanism used by cells in the gut to neutralize harmful toxins may lead to new ways to fight Clostridium difficile, the most common cause of hospital-acquired bacterial infections, researchers said on Sunday.
Tests of an experimental compound that mimics this defense mechanism that has shown promise in the lab and in mouse studies, and the researchers say they are already planning human clinical trials.
C. difficile is an antibiotic-resistant bacterial infection that can cause diarrhea, colitis, the inflammation of the colon. At its worst, it can be fatal.
"This is a $3.5 billion problem in the U.S. alone and it's rising rapidly because of new, even more virulent strains," said Tor Savidge of the University of Texas Medical Branch at Galveston, whose study is being published in the journal Nature Medicine.
"Between 1 to 2 percent of patients who go into the hospital will develop this."
Elderly patients being treated with antibiotics — which kill natural bacteria in the gut and allow invaders such as C. difficile to flourish — are especially vulnerable.
Savidge and colleagues from the University of California, Los Angeles, Case Western Reserve University, Tufts University and the Commonwealth Medical College noticed that in order to squeeze into cells lining the intestine, toxins produced by C. difficile need to chop themselves into smaller bits.
C. difficile accomplishes this through a molecular guillotine called a cysteine protease, which only becomes active when a molecule called InsP6 is present in large concentrations inside a cell.
Once inside the cell, the toxin releases its payload, killing cells that line the intestine and triggering inflammation and diarrhea.
What Savidge's team discovered is that once this process starts, the body releases neutralizing chemicals that gum up the molecular guillotine, preventing the toxins from being chopped up and damaging the cell.
Inspired by this natural mechanism, the team developed a treatment that mimics this process, shutting down the guillotine and preventing the toxin from damaging the cell.
"If you shut them down before they can interact with the cell we can alleviate the disease."
Mice with C. difficile who were treated with the drug were became less ill and were more likely to survive their infections than untreated mice.
Currently, patients who get these infections are treated with antibiotics, which contributes to the problem of antibiotic resistance.
But this new treatment would simply keep the toxins from making people sick, allowing the normal, protective gut bacteria to remain intact.
"This may prove to be an alternative to antibiotics," Savidge said, but much more work is needed.
"This needs to be confirmed with additional studies and additional groups will need to confirm it as well."
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