New study reveals 3D structure of toxin responsible for toxin C. Diff

A new study, led by researchers at the University of California at Irvine (UCI), reveals the much sought-after three-dimensional structure of a toxin primarily responsible for the devastating infection with Clostridium difficile (CDI).

Posted today in Nature Structural and Molecular BiologyThe study titled "Structure of Clostridium difficile Complete Toxin B" highlights the weaknesses of TcdB, one of the toxins secreted by Clostridium difficile (C. diff) and the leading cause of CDI.

This is the first time we could directly see the 3D structure of the gigantic TcdB holotoxin at a resolution close to the atom. It is interesting to note that this toxin has the form of a question mark from a certain angle. This is a major issue for us as we look for ways to fight toxin and CDI. "

Rongsheng Jin, PhD, Professor, Department of Physiology and Biophysics, Faculty of Medicine, UCI

Jin is also the main author of the study

Also included in the study, the team showed how three antibodies could neutralize the TcdB, thus revealing the intrinsic vulnerabilities of the TcdB toxin, which could be exploited to develop new treatments and vaccines for the treatment of cancer. # 39; DCI.

C. diff is an opportunistic pathogen that develops in the colon when the gut microbiota is disrupted, often seen in critically ill or elderly patients, in hospitals or long-term care facilities. ICD has become the most common cause of antibiotic-badociated diarrhea and gastroenteritis-related deaths in developed countries, accounting for half a million cases and 29,000 deaths per year in the United States. It is ranked among the top three "urgent threats" by CDC. The current standard of TIA treatment involves treatments using broad-spectrum antibiotics that reduce the level of C. diff bacteria, but also destroy the good bacteria in the intestine and disrupt the normal intestinal microbiome. This approach often leads to frequent recurrence of the disease (up to 35%).

The Food and Drug Administration (FDA) has recently issued a warning regarding an experimental fecal microbiota for transplantation (FMT) procedure for the treatment of ICD following the death of a patient at the same time. 39, a clinical trial. In another action, the FDA approved Bezlotoxumab, a human monoclonal antibody that neutralizes TcdB, as a prevention against recurrent infections.

"There is still a desperate need for more powerful and less expensive treatments against ICD," said Jin. "The good news is that the TcdB 3D framework we have identified is literally providing a model for the development of new generation vaccines and treatments that have increased potency and expanded reactivity across different strains of C. diff."

The UCI team is already working on a new vaccine based on the new structure. The first studies show promising results, which Jin hopes to publish soon. In the meantime, the Regents of the University of California have filed a patent for their work.