Researchers Identify C. Diff Gene Enabling Bacteria to Bind to Gut

Study findings could offer a new approach to the toxin-based approach of other C. difficile vaccines in development.

In a potential breakthrough in the development of a Clostridioides difficile (C. diff) vaccine, researchers have identified a gene responsible for producing a protein that helps bind the bacteria to the gut of patients, according to a University of Exeter press release.

No vaccine for C. diff is currently in widespread use, although some toxin-based vaccines are being investigated. In 2017, Sanofi ended its efforts to find a toxin-based C. diff vaccine after many years of work because of a low probability of success. The alternative to toxin-based vaccines is an adhesion-targeting approach, such as the one identified in the current study.

The findings could offer a new approach because the C. diff bacteria must bind to the gut to produce the toxin that causes the illness. The researchers noted that infection with C. diff is frequently a result of treatment with antibiotics, which disrupt the natural gut bacteria.

“With other bacteria missing, C. diff can attach to the gut and release a toxin that causes symptoms including diarrhea,” said Stephen Michell, PhD, BSc, a senior lecturer at the University of Exeter, in a press release. “We identified a gene—CD0873—that generates a protein that helps C. diff bind to the gut. This binding is thought to be key for C. diff infections, so if we can prevent adhesion of bacteria then there’s a real possibility of preventing this disease.”

Investigators immunized mice with the CD0873 protein in isolation and found a “strong” immune response, according to the study. After being exposed to C. diff, these mice were unaffected, whereas non-immunized mice became sick and lost an average of approximately 10% of their body weight.

Researchers at the University of Paris-Sud conducted the experiments and noted that mice develop antibodies when immunized with the CD0873 protein. Other researchers then mapped the 3D molecular structure of CD0873 at high resolution using a high-brightness X-ray beam.

“A vaccine that stops the C. diff sticking to the gut wall and so stops it making the gut its new home, would then stop the bug being able to cause diarrhea or infection,” said Ray Sheridan, a consultant physician at the Royal Devon & Exeter Hospital, in the press release. “This would need to go through clinical trials, but if it worked it would potentially prevent C. diff infection altogether.”

REFERENCE

Advance in search for new Clostridioides difficile vaccine. News release. EurekAlert. October 25, 2019. Accessed July 20, 2021. https://www.eurekalert.org/pub_releases/2019-10/uoe-ais102319.php