29 October 2020

Yeast vs. clostridium

Scientists cured severe intestinal inflammation with GM yeast

Sergey Vasiliev, Naked Science

The abuse of antibiotics can destroy the natural symbiotic intestinal microflora, against which the bacteria Clostridioides difficile begin to multiply here. These clostridia cause pseudomembranous enterocolitis – a severe and poorly curable inflammation of the colon, which can even end in death.

To get rid of the disease, they are even trying to use an experimental procedure of fecal transplantation, which contributes to the normalization of the microflora. And a new work by Hanping Feng and his colleagues from the University of Maryland promises to create "yeast tablets" that destroy C. diff. The scientists presented it in an article published in the journal Science Translational Medicine (Chen et al., A probiotic yeast-based immunotherapy against Clostridioides difficile infection).

It is worth saying that in some particularly severe cases, patients with enterocolitis have to inject intravenously a cocktail of monoclonal antibodies. They neutralize TcdA and TcdB toxins, which are the main weapons of pathogenic clostridium. However, such drugs are difficult to manufacture and expensive. Therefore, scientists decided to entrust this task to "living factories" – yeast cells Saccharomyces boulardii. Their preparations have long been used in medicine to normalize the work of the intestine and have repeatedly proven their safety.

Now, researchers have designed a new antibody protein adapted for production in yeast cells and capable of attacking both clostridium toxins. This was demonstrated by introducing a mixture of such proteins and toxins to experimental mice that successfully survived a lethal dose of poison. Then the scientists tested the protective effect of live GM yeast, in whose DNA a gene was introduced for the synthesis of the desired antibody.

To do this, rodents were disturbed by microflora with the help of antibiotics, and then injected with clostridium spores. Animals from the experimental group received a daily dose of GM yeast three days before the injection and successfully survived the infection. Meanwhile, more than half of the control group animals treated with ordinary yeast or just an aqueous solution died of infection, and an autopsy confirmed severe intestinal damage.

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