By Aimee Keenan-Greene

University of Texas researchers in Galveston  have discovered a key mechanism intestinal cells use to defend against the antibiotic-resistant hospital acquired infection (HAI) known as Clostridium difficile - which affects one percent of all hospital patients and can cause symptoms from diarrhea to life-threatening bowel inflammation.

The American Journal of Infection Control (2009) reported an estimated 13 of  every 1,000 hospital inpatients had C. diff - 20 times more than previous estimates.

Scientists investigating cellular responses to two powerful toxins generated by the bacteria Clostridium difficile, found those toxins wreak havoc on cell structural proteins and biochemical communications networks, eventually killing healthy cells.

In order to do this damage, the toxins have to get into the cell, and that means passing through the protective membrane that surrounds it.

The news, published online today in Nature Medicine, explains that on the molecular scale, C. difficile toxin proteins are large.  They have to "cleave" so a smaller piece can slip through the membrane 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  present at much higher levels inside the cell than outside.

"It's sort of like a sensor mechanism that detects when it's in a cell — the toxins say, InsP6 is here, it's time to cleave," says University of Texas Medical Branch at Galveston associate professor Tor Savidge, lead author of a paper, "We've identified a previously unknown protective response that activates after the toxins have induced gut inflammation, in which the host uses a process called nitrosylation to shut down the cysteine protease and prevent cleavage." 

A toxin that's unable to cleave stays stuck in the cell membrane, incapable of attacking the cell.

"The author is in public relations and communications and is affiliated with the Pear Health Company."