Clostridium difficile is a Gram positive, rod-shaped bacterium commonly found in the soil. However, a small number of people, about
1 in 20, also house
C. difficile in their guts. This usually isn’t a problem, but the bacteria can produce toxins that cause severe cases of colitis, diarrhea, and sometimes death. These infections typically occur in cases where the normal gut flora has been depleted by antibiotics, allowing
C. difficile to “take over”.
Since antibiotics often promote
C. difficile infections, they aren’t much use in combating these bacteria. This has left researchers searching for other treatment options, and scientists at Stanford University School of Medicine have taken a unique approach.
Instead of searching for a way to kill
C. difficile directly, Matthew Bogyo, Ph.D., used a small molecule called
ebselen to disarm
C. difficile toxins. These toxins enter the cells lining the gut and induce an inflammatory response, resulting in colitis and diarrhea. This proinflammatory response also prevents the normal flora from repopulating the gut.
Bogyo and colleagues
showed that ebselen had a direct effect on the activity of
C. difficile toxins by incubating purified toxin with or without ebselen, and then injecting the mixtures into mice. After three days, all of the mice injected with toxin alone died, while the mice injected with the ebselen and toxin mixture survived. Bogyo then tested a more clinically relevant model of infection. They first treated mice with antibiotics to mimic the conditions under which
C. difficile infections occur. Following antibiotic treatment, they infected mice with a highly virulent, drug-resistant strain of
C. difficile, and treated them orally with ebselen. The mice treated with ebselen survived the infection with little evidence of damage to the colon.
Thus, ebselen both prevented damaging colitis and diarrhea, and allowed the normal flora to outcompete
C. difficile. What’s more, ebselen has already been tested in clinical trials to treat hearing loss in chemotherapy patients. This means ebselen could be on the fast track to treating
C. difficile infections.
Ebselen isn’t the only unique approach to treating
C. difficile. Fecal transplant, as explained in this
video, has been highly successful in treating
C. difficile infections.
Sources:
Science Daily,
Science Translational Medicine, Wikipedia,
Cleveland Clinic
