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“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[.]” … “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 … 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 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,” Savidge said. “But 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 researchers used test-tube, cell culture, patient specimens and animal model experiments, along with computer simulations of molecular interactions, to thoroughly explore this response — and to successfully devise a way to mimic it for therapeutic purposes.
“Think of these toxins as missiles that the bacteria is producing to go off and detonate inside the cell,” Savidge said. “One way to defend against missiles is to send out signals that trick them into either disarming their sensory mechanisms or get them to prematurely detonate.”
Any take-home lessons for MC treatment here?
Anything that effectively prevents the C. diff bacteria from attaching to the gut wall will certainly serve to minimize any exposure to toxins, because if they can't attach, the bacteria and their toxins will just be harmlessly washed downstream. L-glutamine might have some capacity to do that - it certainly seems to work for E. coli, at least. Even something as simple as Pepto-Bismol can help to prevent attaching, and, of course, theoretically, at least, flooding the gut with a "good" probiotic should accomplish the same thing, so long as a high enough bacteria count sufficient to do the job is always present, (IOW, replenished regularly).